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Neurotrophins in the Regulation of Cellular Survival and Death

  • Claire Ceni
  • Nicolas Unsain
  • Michele P. Zeinieh
  • Philip A. Barker
Chapter
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 220)

Abstract

The neurotrophins play crucial roles regulating survival and apoptosis in the developing and injured nervous system. The four neurotrophins exert profound and crucial survival effects on developing peripheral neurons, and their expression and action is intimately tied to successful innervation of peripheral targets. In the central nervous system, they are dispensable for neuronal survival during development but support neuronal survival after lesion or other forms of injury. Neurotrophins also regulate apoptosis of both peripheral and central neurons, and we now recognize that there are regulatory advantages to having the same molecules regulate life and death decisions. This chapter examines the biological contexts in which these events take place and highlights the specific ligands, receptors, and signaling mechanisms that allow them to occur.

Keywords

Proneurotrophins p75NTR Sortilin Retrograde signaling Tumor cells Apoptosis Death domains NF-kB Interleukin-1 receptor associated kinase (IRAK) RIP2 Receptor-interacting serine/Threonine-protein kinase 2 (RIP2) Neurotrophin receptor interacting factor (NRIF) Neurotrophin receptor-interacting MAGE homolog (NRAGE) 

References

  1. Agerman K, Baudet C, Fundin B, Willson C, Ernfors P (2000) Attenuation of a caspase-3 dependent cell death in NT4- and p75-deficient embryonic sensory neurons. Mol Cell Neurosci 16(3):258–268PubMedGoogle Scholar
  2. Airaksinen MS, Koltzenburg M, Lewin GR, Masu Y, Helbig C, Wolf E, Brem G, Toyka KV, Thoenen H, Meyer M (1996) Specific subtypes of cutaneous mechanoreceptors require neurotrophin-3 following peripheral target innervation. Neuron 16(2):287–295PubMedGoogle Scholar
  3. Albers KM, Wright DE, Davis BM (1994) Overexpression of nerve growth factor in epidermis of transgenic mice causes hypertrophy of the peripheral nervous system. J Neurosci 14(3 Pt 2):1422–1432PubMedGoogle Scholar
  4. Alcantara S, Frisen J, del Rio JA, Soriano E, Barbacid M, Silos-Santiago I (1997) TrkB signaling is required for postnatal survival of CNS neurons and protects hippocampal and motor neurons from axotomy-induced cell death. J Neurosci 17(10):3623–3633PubMedGoogle Scholar
  5. Arevalo MA, Rodriguez-Tebar A (2006) Activation of casein kinase II and inhibition of phosphatase and tensin homologue deleted on chromosome 10 phosphatase by nerve growth factor/p75NTR inhibit glycogen synthase kinase-3beta and stimulate axonal growth. Mol Biol Cell 17(8):3369–3377PubMedCentralPubMedGoogle Scholar
  6. Bai Y, Dergham P, Nedev H, Xu J, Galan A, Rivera JC, ZhiHua S, Mehta HM, Woo SB, Sarunic MV, Neet KE, Saragovi HU (2010) Chronic and acute models of retinal neurodegeneration TrkA activity are neuroprotective whereas p75NTR activity is neurotoxic through a paracrine mechanism. J Biol Chem 285(50):39392–39400PubMedCentralPubMedGoogle Scholar
  7. Balthasar N, Coppari R, McMinn J, Liu SM, Lee CE, Tang V, Kenny CD, McGovern RA, Chua SC Jr, Elmquist JK, Lowell BB (2004) Leptin receptor signaling in POMC neurons is required for normal body weight homeostasis. Neuron 42(6):983–991PubMedGoogle Scholar
  8. Bamji SX, Majdan M, Pozniak CD, Belliveau DJ, Aloyz R, Kohn J, Causing CG, Miller FD (1998) The p75 neurotrophin receptor mediates neuronal apoptosis and is essential for naturally occurring sympathetic neuron death. J Cell Biol 140(4):911–923PubMedCentralPubMedGoogle Scholar
  9. Baquet ZC, Gorski JA, Jones KR (2004) Early striatal dendrite deficits followed by neuron loss with advanced age in the absence of anterograde cortical brain-derived neurotrophic factor. J Neurosci 24(17):4250–4258PubMedGoogle Scholar
  10. Barde YA (1989) Trophic factors and neuronal survival. Neuron 2(6):1525–1534PubMedGoogle Scholar
  11. Barde YA, Edgar D, Thoenen H (1982) Purification of a new neurotrophic factor from mammalian brain. EMBO J 1(5):549–553PubMedCentralPubMedGoogle Scholar
  12. Barker PA (2007) High affinity not in the vicinity? Neuron 53(1):1–4PubMedGoogle Scholar
  13. Barker PA, Shooter EM (1994) Disruption of NGF binding to the low affinity neurotrophin receptor p75LNTR reduces NGF binding to TrkA on PC12 cells. Neuron 13(1):203–215PubMedGoogle Scholar
  14. Barrett GL, Bartlett PF (1994) The p75 nerve growth factor receptor mediates survival or death depending on the stage of sensory neuron development. Proc Natl Acad Sci USA 91(14):6501–6505PubMedCentralPubMedGoogle Scholar
  15. Beattie MS, Harrington AW, Lee R, Kim JY, Boyce SL, Longo FM, Bresnahan JC, Hempstead BL, Yoon SO (2002) ProNGF induces p75-mediated death of oligodendrocytes following spinal cord injury. Neuron 36(3):375–386PubMedCentralPubMedGoogle Scholar
  16. Bergmann I, Priestley JV, McMahon SB, Brocker EB, Toyka KV, Koltzenburg M (1997) Analysis of cutaneous sensory neurons in transgenic mice lacking the low affinity neurotrophin receptor p75. Eur J Neurosci 9(1):18–28PubMedGoogle Scholar
  17. Bertrand MJ, Kenchappa RS, Andrieu D, Leclercq-Smekens M, Nguyen HN, Carter BD, Muscatelli F, Barker PA, De Backer O (2008) NRAGE, a p75NTR adaptor protein, is required for developmental apoptosis in vivo. Cell Death Differ 15(12):1921–1929PubMedCentralPubMedGoogle Scholar
  18. Bhakar AL, Roux PP, Lachance C, Kryl D, Zeindler C, Barker PA (1999) The p75 neurotrophin receptor (p75NTR) alters tumor necrosis factor-mediated NF-kappaB activity under physiological conditions, but direct p75NTR-mediated NF-kappaB activation requires cell stress. J Biol Chem 274(30):21443–21449PubMedGoogle Scholar
  19. Bhakar AL, Howell JL, Paul CE, Salehi AH, Becker EB, Said F, Bonni A, Barker PA (2003) Apoptosis induced by p75NTR overexpression requires Jun kinase-dependent phosphorylation of Bad. J Neurosci 23(36):11373–11381PubMedGoogle Scholar
  20. Bhattacharyya A, Watson FL, Pomeroy SL, Zhang YZ, Stiles CD, Segal RA (2002) High-resolution imaging demonstrates dynein-based vesicular transport of activated Trk receptors. J Neurobiol 51(4):302–312PubMedGoogle Scholar
  21. Bibel M, Hoppe E, Barde YA (1999) Biochemical and functional interactions between the neurotrophin receptors trk and p75NTR. EMBO J 18(3):616–622PubMedCentralPubMedGoogle Scholar
  22. Bothwell M (1995) Functional interactions of neurotrophins and neurotrophin receptors. Annu Rev Neurosci 18:223–253PubMedGoogle Scholar
  23. Brann AB, Tcherpakov M, Williams IM, Futerman AH, Fainzilber M (2002) Nerve growth factor-induced p75-mediated death of cultured hippocampal neurons is age-dependent and transduced through ceramide generated by neutral sphingomyelinase. J Biol Chem 277(12):9812–9818PubMedGoogle Scholar
  24. Brodeur GM, Minturn JE, Ho R, Simpson AM, Iyer R, Varela CR, Light JE, Kolla V, Evans AE (2009) Trk receptor expression and inhibition in neuroblastomas. Clin Cancer Res 15(10):3244–3250PubMedGoogle Scholar
  25. Brunet A, Bonni A, Zigmond MJ, Lin MZ, Juo P, Hu LS, Anderson MJ, Arden KC, Blenis J, Greenberg ME (1999) Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell 96(6):857–868PubMedGoogle Scholar
  26. Brunet A, Datta SR, Greenberg ME (2001) Transcription-dependent and -independent control of neuronal survival by the PI3K-Akt signaling pathway. Curr Opin Neurobiol 11(3):297–305PubMedGoogle Scholar
  27. Buchman VL, Davies AM (1993) Different neurotrophins are expressed and act in a developmental sequence to promote the survival of embryonic sensory neurons. Development 118(3):989–1001PubMedGoogle Scholar
  28. Bui NT, Konig HG, Culmsee C, Bauerbach E, Poppe M, Krieglstein J, Prehn JH (2002) p75 neurotrophin receptor is required for constitutive and NGF-induced survival signalling in PC12 cells and rat hippocampal neurones. J Neurochem 81(3):594–605PubMedGoogle Scholar
  29. Carter BD, Kaltschmidt C, Kaltschmidt B, Offenhauser N, Bohm-Matthaei R, Baeuerle PA, Barde YA (1996) Selective activation of NF-kappa B by nerve growth factor through the neurotrophin receptor p75. Science 272(5261):542–545PubMedGoogle Scholar
  30. Casaccia-Bonnefil P, Carter BD, Dobrowsky RT, Chao MV (1996) Death of oligodendrocytes mediated by the interaction of nerve growth factor with its receptor p75. Nature 383(6602):716–719PubMedGoogle Scholar
  31. Casademunt E, Carter BD, Benzel I, Frade JM, Dechant G, Barde YA (1999) The zinc finger protein NRIF interacts with the neurotrophin receptor p75(NTR) and participates in programmed cell death. EMBO J 18(21):6050–6061PubMedCentralPubMedGoogle Scholar
  32. Castren E, Zafra F, Thoenen H, Lindholm D (1992) Light regulates expression of brain-derived neurotrophic factor mRNA in rat visual cortex. Proc Natl Acad Sci USA 89(20):9444–9448PubMedCentralPubMedGoogle Scholar
  33. Ceni C, Kommaddi RP, Thomas R, Vereker E, Liu X, McPherson PS, Ritter B, Barker PA (2010) The p75NTR intracellular domain generated by neurotrophin-induced receptor cleavage potentiates Trk signaling. J Cell Sci 123(Pt 13):2299–2307PubMedGoogle Scholar
  34. Chan JP, Unger TJ, Byrnes J, Rios M (2006a) Examination of behavioral deficits triggered by targeting Bdnf in fetal or postnatal brains of mice. Neuroscience 142(1):49–58PubMedGoogle Scholar
  35. Chan JR, Jolicoeur C, Yamauchi J, Elliott J, Fawcett JP, Ng BK, Cayouette M (2006b) The polarity protein Par-3 directly interacts with p75NTR to regulate myelination. Science 314(5800):832–836PubMedGoogle Scholar
  36. Chan JP, Cordeira J, Calderon GA, Iyer LK, Rios M (2008) Depletion of central BDNF in mice impedes terminal differentiation of new granule neurons in the adult hippocampus. Mol Cell Neurosci 39(3):372–383PubMedCentralPubMedGoogle Scholar
  37. Chen KS, Nishimura MC, Armanini MP, Crowley C, Spencer SD, Phillips HS (1997) Disruption of a single allele of the nerve growth factor gene results in atrophy of basal forebrain cholinergic neurons and memory deficits. J Neurosci 17(19):7288–7296PubMedGoogle Scholar
  38. Chou TT, Trojanowski JQ, Lee VM (2000) A novel apoptotic pathway induced by nerve growth factor-mediated TrkA activation in medulloblastoma. J Biol Chem 275(1):565–570PubMedGoogle Scholar
  39. Clary DO, Reichardt LF (1994) An alternatively spliced form of the nerve growth factor receptor TrkA confers an enhanced response to neurotrophin 3. Proc Natl Acad Sci USA 91(23):11133–11137PubMedCentralPubMedGoogle Scholar
  40. Conover JC, Erickson JT, Katz DM, Bianchi LM, Poueymirou WT, McClain J, Pan L, Helgren M, Ip NY, Boland P et al (1995) Neuronal deficits, not involving motor neurons, in mice lacking BDNF and/or NT4. Nature 375(6528):235–238PubMedGoogle Scholar
  41. Copray JC, Brouwer N (1994) Selective expression of neurotrophin-3 messenger RNA in muscle spindles of the rat. Neuroscience 63(4):1125–1135PubMedGoogle Scholar
  42. Cosgaya JM, Chan JR, Shooter EM (2002) The neurotrophin receptor p75NTR as a positive modulator of myelination. Science 298(5596):1245–1248PubMedGoogle Scholar
  43. Crowley C, Spencer SD, Nishimura MC, Chen KS, Pitts-Meek S, Armanini MP, Ling LH, McMahon SB, Shelton DL, Levinson AD et al (1994) Mice lacking nerve growth factor display perinatal loss of sensory and sympathetic neurons yet develop basal forebrain cholinergic neurons. Cell 76(6):1001–1011PubMedGoogle Scholar
  44. Dadakhujaev S, Jung EJ, Noh HS, Hah YS, Kim CJ, Kim DR (2009) Interplay between autophagy and apoptosis in TrkA-induced cell death. Autophagy 5(1):103–105PubMedGoogle Scholar
  45. Datta SR, Dudek H, Tao X, Masters S, Fu H, Gotoh Y, Greenberg ME (1997) Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell 91(2):231–241PubMedGoogle Scholar
  46. Davies AM, Lee KF, Jaenisch R (1993) p75-deficient trigeminal sensory neurons have an altered response to NGF but not to other neurotrophins. Neuron 11(4):565–574PubMedGoogle Scholar
  47. Dixon SJ, MacDonald JI, Robinson KN, Kubu CJ, Meakin SO (2006) Trk receptor binding and neurotrophin/fibroblast growth factor (FGF)-dependent activation of the FGF receptor substrate (FRS)-3. Biochim Biophys Acta 1763(4):366–380PubMedGoogle Scholar
  48. Epa WR, Markovska K, Barrett GL (2004) The p75 neurotrophin receptor enhances TrkA signalling by binding to Shc and augmenting its phosphorylation. J Neurochem 89(2):344–353PubMedGoogle Scholar
  49. Ernfors P (2001) Local and target-derived actions of neurotrophins during peripheral nervous system development. Cell Mol Life Sci 58(8):1036–1044PubMedGoogle Scholar
  50. Ernfors P, Lee KF, Jaenisch R (1994a) Mice lacking brain-derived neurotrophic factor develop with sensory deficits. Nature 368(6467):147–150PubMedGoogle Scholar
  51. Ernfors P, Lee KF, Kucera J, Jaenisch R (1994b) Lack of neurotrophin-3 leads to deficiencies in the peripheral nervous system and loss of limb proprioceptive afferents. Cell 77(4):503–512PubMedGoogle Scholar
  52. Esposito D, Patel P, Stephens RM, Perez P, Chao MV, Kaplan DR, Hempstead BL (2001) The cytoplasmic and transmembrane domains of the p75 and Trk A receptors regulate high affinity binding to nerve growth factor. J Biol Chem 276(35):32687–32695PubMedGoogle Scholar
  53. Farinas I (1999) Neurotrophin actions during the development of the peripheral nervous system. Microsc Res Tech 45(4–5):233–242PubMedGoogle Scholar
  54. Farinas I, Jones KR, Backus C, Wang XY, Reichardt LF (1994) Severe sensory and sympathetic deficits in mice lacking neurotrophin-3. Nature 369(6482):658–661PubMedGoogle Scholar
  55. Farinas I, Yoshida CK, Backus C, Reichardt LF (1996) Lack of neurotrophin-3 results in death of spinal sensory neurons and premature differentiation of their precursors. Neuron 17(6):1065–1078PubMedCentralPubMedGoogle Scholar
  56. Farinas I, Wilkinson GA, Backus C, Reichardt LF, Patapoutian A (1998) Characterization of neurotrophin and Trk receptor functions in developing sensory ganglia: direct NT-3 activation of TrkB neurons in vivo. Neuron 21(2):325–334PubMedCentralPubMedGoogle Scholar
  57. Ferri CC, Moore FA, Bisby MA (1998) Effects of facial nerve injury on mouse motoneurons lacking the p75 low-affinity neurotrophin receptor. J Neurobiol 34(1):1–9PubMedGoogle Scholar
  58. Frade JM, Barde YA (1999) Genetic evidence for cell death mediated by nerve growth factor and the neurotrophin receptor p75 in the developing mouse retina and spinal cord. Development 126(4):683–690PubMedGoogle Scholar
  59. Frade JM, Rodriguez-Tebar A, Barde YA (1996) Induction of cell death by endogenous nerve growth factor through its p75 receptor. Nature 383(6596):166–168PubMedGoogle Scholar
  60. Friedman WJ (2000) Neurotrophins induce death of hippocampal neurons via the p75 receptor. J Neurosci 20(17):6340–6346PubMedGoogle Scholar
  61. Fundin BT, Silos-Santiago I, Ernfors P, Fagan AM, Aldskogius H, DeChiara TM, Phillips HS, Barbacid M, Yancopoulos GD, Rice FL (1997) Differential dependency of cutaneous mechanoreceptors on neurotrophins, trk receptors, and P75 LNGFR. Dev Biol 190(1):94–116PubMedGoogle Scholar
  62. Gao X, Chen J (2009) Conditional knockout of brain-derived neurotrophic factor in the hippocampus increases death of adult-born immature neurons following traumatic brain injury. J Neurotrauma 26(8):1325–1335PubMedGoogle Scholar
  63. Gentry JJ, Casaccia-Bonnefil P, Carter BD (2000) Nerve growth factor activation of nuclear factor kappaB through its p75 receptor is an anti-apoptotic signal in RN22 schwannoma cells. J Biol Chem 275(11):7558–7565PubMedGoogle Scholar
  64. Giehl KM, Tetzlaff W (1996) BDNF and NT-3, but not NGF, prevent axotomy-induced death of rat corticospinal neurons in vivo. Eur J Neurosci 8(6):1167–1175PubMedGoogle Scholar
  65. Giehl KM, Schutte A, Mestres P, Yan Q (1998) The survival-promoting effect of glial cell line-derived neurotrophic factor on axotomized corticospinal neurons in vivo is mediated by an endogenous brain-derived neurotrophic factor mechanism. J Neurosci 18(18):7351–7360PubMedGoogle Scholar
  66. Giehl KM, Rohrig S, Bonatz H, Gutjahr M, Leiner B, Bartke I, Yan Q, Reichardt LF, Backus C, Welcher AA, Dethleffsen K, Mestres P, Meyer M (2001) Endogenous brain-derived neurotrophic factor and neurotrophin-3 antagonistically regulate survival of axotomized corticospinal neurons in vivo. J Neurosci 21(10):3492–3502PubMedCentralPubMedGoogle Scholar
  67. Ginty DD, Segal RA (2002) Retrograde neurotrophin signaling: Trk-ing along the axon. Curr Opin Neurobiol 12(3):268–274PubMedGoogle Scholar
  68. Gjerstad MD, Tandrup T, Koltzenburg M, Jakobsen J (2002) Predominant neuronal B-cell loss in L5 DRG of p75 receptor-deficient mice. J Anat 200(Pt 1):81–87PubMedGoogle Scholar
  69. Gorski JA, Zeiler SR, Tamowski S, Jones KR (2003) Brain-derived neurotrophic factor is required for the maintenance of cortical dendrites. J Neurosci 23(17):6856–6865PubMedGoogle Scholar
  70. Gotz R, Koster R, Winkler C, Raulf F, Lottspeich F, Schartl M, Thoenen H (1994) Neurotrophin-6 is a new member of the nerve growth factor family. Nature 372(6503):266–269PubMedGoogle Scholar
  71. Green SH, Greene LA (1986) A single Mr approximately 103,000 125I-beta-nerve growth factor-affinity-labeled species represents both the low and high affinity forms of the nerve growth factor receptor. J Biol Chem 261(32):15316–15326PubMedGoogle Scholar
  72. Greene LA, Tischler AS (1976) Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth factor. Proc Natl Acad Sci USA 73(7):2424–2428PubMedCentralPubMedGoogle Scholar
  73. Grimes ML, Zhou J, Beattie EC, Yuen EC, Hall DE, Valletta JS, Topp KS, LaVail JH, Bunnett NW, Mobley WC (1996) Endocytosis of activated TrkA: evidence that nerve growth factor induces formation of signaling endosomes. J Neurosci 16(24):7950–7964PubMedGoogle Scholar
  74. Grimes ML, Beattie E, Mobley WC (1997) A signaling organelle containing the nerve growth factor-activated receptor tyrosine kinase, TrkA. Proc Natl Acad Sci USA 94(18):9909–9914PubMedCentralPubMedGoogle Scholar
  75. Grivennikov SI, Kuprash DV, Liu ZG, Nedospasov SA (2006) Intracellular signals and events activated by cytokines of the tumor necrosis factor superfamily: from simple paradigms to complex mechanisms. Int Rev Cytol 252:129–161PubMedGoogle Scholar
  76. Gschwendtner A, Liu Z, Hucho T, Bohatschek M, Kalla R, Dechant G, Raivich G (2003) Regulation, cellular localization, and function of the p75 neurotrophin receptor (p75NTR) during the regeneration of facial motoneurons. Mol Cell Neurosci 24(2):307–322PubMedGoogle Scholar
  77. Gulino A, Arcella A, Giangaspero F (2008) Pathological and molecular heterogeneity of medulloblastoma. Curr Opin Oncol 20(6):668–675PubMedGoogle Scholar
  78. Hallbook F, Ibanez CF, Persson H (1991) Evolutionary studies of the nerve growth factor family reveal a novel member abundantly expressed in Xenopus ovary. Neuron 6(5):845–858PubMedGoogle Scholar
  79. Hamanoue M, Middleton G, Wyatt S, Jaffray E, Hay RT, Davies AM (1999) p75-mediated NF-kappaB activation enhances the survival response of developing sensory neurons to nerve growth factor. Mol Cell Neurosci 14(1):28–40PubMedGoogle Scholar
  80. Hansen K, Wagner B, Hamel W, Schweizer M, Haag F, Westphal M, Lamszus K (2007) Autophagic cell death induced by TrkA receptor activation in human glioblastoma cells. J Neurochem 103(1):259–275PubMedGoogle Scholar
  81. Hantzopoulos PA, Suri C, Glass DJ, Goldfarb MP, Yancopoulos GD (1994) The low affinity NGF receptor, p75, can collaborate with each of the Trks to potentiate functional responses to the neurotrophins. Neuron 13(1):187–201PubMedGoogle Scholar
  82. Harada T, Harada C, Nakayama N, Okuyama S, Yoshida K, Kohsaka S, Matsuda H, Wada K (2000) Modification of glial-neuronal cell interactions prevents photoreceptor apoptosis during light-induced retinal degeneration. Neuron 26(2):533–541PubMedGoogle Scholar
  83. Harel L, Costa B, Tcherpakov M, Zapatka M, Oberthuer A, Hansford LM, Vojvodic M, Levy Z, Chen ZY, Lee FS, Avigad S, Yaniv I, Shi L, Eils R, Fischer M, Brors B, Kaplan DR, Fainzilber M (2009) CCM2 mediates death signaling by the TrkA receptor tyrosine kinase. Neuron 63(5):585–591PubMedGoogle Scholar
  84. Harel L, Costa B, Fainzilber M (2010) On the death Trk. Dev Neurobiol 70(5):298–303PubMedGoogle Scholar
  85. Harrington AW, St Hillaire C, Zweifel LS, Glebova NO, Philippidou P, Halegoua S, Ginty DD (2011) Recruitment of actin modifiers to TrkA endosomes governs retrograde NGF signaling and survival. Cell 146(3):421–434PubMedCentralPubMedGoogle Scholar
  86. Harrison SM, Davis BM, Nishimura M, Albers KM, Jones ME, Phillips HS (2004) Rescue of NGF-deficient mice I: transgenic expression of NGF in skin rescues mice lacking endogenous NGF. Brain Res Mol Brain Res 122(2):116–125PubMedGoogle Scholar
  87. Hempstead BL (2006) Dissecting the diverse actions of pro- and mature neurotrophins. Curr Alzheimer Res 3(1):19–24PubMedGoogle Scholar
  88. Hempstead BL, Martin-Zanca D, Kaplan DR, Parada LF, Chao MV (1991) High-affinity NGF binding requires coexpression of the trk proto-oncogene and the low-affinity NGF receptor. Nature 350(6320):678–683PubMedGoogle Scholar
  89. Hendry IA, Stockel K, Thoenen H, Iversen LL (1974) The retrograde axonal transport of nerve growth factor. Brain Res 68(1):103–121PubMedGoogle Scholar
  90. Hisata S, Sakisaka T, Baba T, Yamada T, Aoki K, Matsuda M, Takai Y (2007) Rap1-PDZ-GEF1 interacts with a neurotrophin receptor at late endosomes, leading to sustained activation of Rap1 and ERK and neurite outgrowth. J Cell Biol 178(5):843–860PubMedCentralPubMedGoogle Scholar
  91. Hohn A, Leibrock J, Bailey K, Barde YA (1990) Identification and characterization of a novel member of the nerve growth factor/brain-derived neurotrophic factor family. Nature 344(6264):339–341PubMedGoogle Scholar
  92. Howe CL, Valletta JS, Rusnak AS, Mobley WC (2001) NGF signaling from clathrin-coated vesicles: evidence that signaling endosomes serve as a platform for the Ras-MAPK pathway. Neuron 32(5):801–814PubMedGoogle Scholar
  93. Hu B, Yip HK, So KF (1998) Localization of p75 neurotrophin receptor in the retina of the adult SD rat: an immunocytochemical study at light and electron microscopic levels. Glia 24(2):187–197PubMedGoogle Scholar
  94. Huang EJ, Reichardt LF (2001) Neurotrophins: roles in neuronal development and function. Annu Rev Neurosci 24:677–736PubMedCentralPubMedGoogle Scholar
  95. Hubbard SR, Miller WT (2007) Receptor tyrosine kinases: mechanisms of activation and signaling. Curr Opin Cell Biol 19(2):117–123PubMedCentralPubMedGoogle Scholar
  96. Hughes AL, Messineo-Jones D, Lad SP, Neet KE (2001) Distinction between differentiation, cell cycle, and apoptosis signals in PC12 cells by the nerve growth factor mutant delta9/13, which is selective for the p75 neurotrophin receptor. J Neurosci Res 63(1):10–19PubMedGoogle Scholar
  97. Ip NY, Ibanez CF, Nye SH, McClain J, Jones PF, Gies DR, Belluscio L, Le Beau MM, Espinosa R 3rd, Squinto SP et al (1992) Mammalian neurotrophin-4: structure, chromosomal localization, tissue distribution, and receptor specificity. Proc Natl Acad Sci USA 89(7):3060–3064PubMedCentralPubMedGoogle Scholar
  98. Ito H, Nomoto H, Furukawa S (2003) Growth arrest of PC12 cells by nerve growth factor is dependent on the phosphatidylinositol 3-kinase/Akt pathway via p75 neurotrophin receptor. J Neurosci Res 72(2):211–217PubMedGoogle Scholar
  99. Jansen P, Giehl K, Nyengaard JR, Teng K, Lioubinski O, Sjoegaard SS, Breiderhoff T, Gotthardt M, Lin F, Eilers A, Petersen CM, Lewin GR, Hempstead BL, Willnow TE, Nykjaer A (2007) Roles for the pro-neurotrophin receptor sortilin in neuronal development, aging and brain injury. Nat Neurosci 10(11):1449–1457PubMedGoogle Scholar
  100. Jiang Y, Nyengaard JR, Zhang JS, Jakobsen J (2004) Selective loss of calcitonin gene-related Peptide-expressing primary sensory neurons of the a-cell phenotype in early experimental diabetes. Diabetes 53(10):2669–2675PubMedGoogle Scholar
  101. Jing S, Tapley P, Barbacid M (1992) Nerve growth factor mediates signal transduction through trk homodimer receptors. Neuron 9(6):1067–1079PubMedGoogle Scholar
  102. Jones KR, Farinas I, Backus C, Reichardt LF (1994) Targeted disruption of the BDNF gene perturbs brain and sensory neuron development but not motor neuron development. Cell 76(6):989–999PubMedCentralPubMedGoogle Scholar
  103. Jung EJ, Kim DR (2008) Apoptotic cell death in TrkA-overexpressing cells: kinetic regulation of ERK phosphorylation and caspase-7 activation. Mol Cells 26(1):12–17PubMedGoogle Scholar
  104. Kane LP, Shapiro VS, Stokoe D, Weiss A (1999) Induction of NF-kappaB by the Akt/PKB kinase. Curr Biol 9(11):601–604PubMedGoogle Scholar
  105. Kantari C, Walczak H (2011) Caspase-8 and bid: caught in the act between death receptors and mitochondria. Biochim Biophys Acta 1813(4):558–563PubMedGoogle Scholar
  106. Kaplan DR, Miller FD (2000) Neurotrophin signal transduction in the nervous system. Curr Opin Neurobiol 10(3):381–391PubMedGoogle Scholar
  107. Kaplan DR, Hempstead BL, Martin-Zanca D, Chao MV, Parada LF (1991) The trk proto-oncogene product: a signal transducing receptor for nerve growth factor. Science 252(5005):554–558PubMedGoogle Scholar
  108. Kenchappa RS, Zampieri N, Chao MV, Barker PA, Teng HK, Hempstead BL, Carter BD (2006) Ligand-dependent cleavage of the P75 neurotrophin receptor is necessary for NRIF nuclear translocation and apoptosis in sympathetic neurons. Neuron 50(2):219–232PubMedGoogle Scholar
  109. Kenchappa RS, Tep C, Korade Z, Urra S, Bronfman FC, Yoon SO, Carter BD (2010) p75 neurotrophin receptor-mediated apoptosis in sympathetic neurons involves a biphasic activation of JNK and up-regulation of tumor necrosis factor-alpha-converting enzyme/ADAM17. J Biol Chem 285(26):20358–20368PubMedCentralPubMedGoogle Scholar
  110. Khursigara G, Orlinick JR, Chao MV (1999) Association of the p75 neurotrophin receptor with TRAF6. J Biol Chem 274(5):2597–2600PubMedGoogle Scholar
  111. Khursigara G, Bertin J, Yano H, Moffett H, DiStefano PS, Chao MV (2001) A prosurvival function for the p75 receptor death domain mediated via the caspase recruitment domain receptor-interacting protein 2. J Neurosci 21(16):5854–5863PubMedGoogle Scholar
  112. Kim T, Hempstead BL (2009) NRH2 is a trafficking switch to regulate sortilin localization and permit proneurotrophin-induced cell death. EMBO J 28(11):1612–1623PubMedCentralPubMedGoogle Scholar
  113. Klein R, Jing SQ, Nanduri V, O’Rourke E, Barbacid M (1991) The trk proto-oncogene encodes a receptor for nerve growth factor. Cell 65(1):189–197PubMedGoogle Scholar
  114. Klein R, Silos-Santiago I, Smeyne RJ, Lira SA, Brambilla R, Bryant S, Zhang L, Snider WD, Barbacid M (1994) Disruption of the neurotrophin-3 receptor gene trkC eliminates la muscle afferents and results in abnormal movements. Nature 368(6468):249–251PubMedGoogle Scholar
  115. Korhonen JM, Said FA, Wong AJ, Kaplan DR (1999) Gab1 mediates neurite outgrowth, DNA synthesis, and survival in PC12 cells. J Biol Chem 274(52):37307–37314PubMedGoogle Scholar
  116. Kuruvilla R, Zweifel LS, Glebova NO, Lonze BE, Valdez G, Ye H, Ginty DD (2004) A neurotrophin signaling cascade coordinates sympathetic neuron development through differential control of TrkA trafficking and retrograde signaling. Cell 118(2):243–255PubMedGoogle Scholar
  117. Lachance C, Belliveau DJ, Barker PA (1997) Blocking nerve growth factor binding to the p75 neurotrophin receptor on sympathetic neurons transiently reduces trkA activation but does not affect neuronal survival. Neuroscience 81(3):861–871PubMedGoogle Scholar
  118. Lachyankar MB, Condon PJ, Daou MC, De AK, Levine JB, Obermeier A, Ross AH (2003) Novel functional interactions between Trk kinase and p75 neurotrophin receptor in neuroblastoma cells. J Neurosci Res 71(2):157–172PubMedGoogle Scholar
  119. Ladiwala U, Lachance C, Simoneau SJ, Bhakar A, Barker PA, Antel JP (1998) p75 neurotrophin receptor expression on adult human oligodendrocytes: signaling without cell death in response to NGF. J Neurosci 18(4):1297–1304PubMedGoogle Scholar
  120. Lai KO, Fu WY, Ip FC, Ip NY (1998) Cloning and expression of a novel neurotrophin, NT-7, from carp. Mol Cell Neurosci 11(1–2):64–76PubMedGoogle Scholar
  121. Lavoie JF, Lesauteur L, Kohn J, Wong J, Furtoss O, Thiele CJ, Miller FD, Kaplan DR (2005) TrkA induces apoptosis of neuroblastoma cells and does so via a p53-dependent mechanism. J Biol Chem 280(32):29199–29207PubMedGoogle Scholar
  122. Lebrun-Julien F, Duplan L, Pernet V, Osswald I, Sapieha P, Bourgeois P, Dickson K, Bowie D, Barker PA, Di Polo A (2009) Excitotoxic death of retinal neurons in vivo occurs via a non-cell-autonomous mechanism. J Neurosci 29(17):5536–5545PubMedGoogle Scholar
  123. Lee KF, Li E, Huber LJ, Landis SC, Sharpe AH, Chao MV, Jaenisch R (1992) Targeted mutation of the gene encoding the low affinity NGF receptor p75 leads to deficits in the peripheral sensory nervous system. Cell 69(5):737–749PubMedGoogle Scholar
  124. Lee KF, Davies AM, Jaenisch R (1994) p75-deficient embryonic dorsal root sensory and neonatal sympathetic neurons display a decreased sensitivity to NGF. Development 120(4):1027–1033PubMedGoogle Scholar
  125. Lefcort F, Clary DO, Rusoff AC, Reichardt LF (1996) Inhibition of the NT-3 receptor TrkC, early in chick embryogenesis, results in severe reductions in multiple neuronal subpopulations in the dorsal root ganglia. J Neurosci 16(11):3704–3713PubMedGoogle Scholar
  126. Leibrock J, Lottspeich F, Hohn A, Hofer M, Hengerer B, Masiakowski P, Thoenen H, Barde YA (1989) Molecular cloning and expression of brain-derived neurotrophic factor. Nature 341(6238):149–152PubMedGoogle Scholar
  127. Levi-Montalcini R (1987) The nerve growth factor 35 years later. Science 237(4819):1154–1162PubMedGoogle Scholar
  128. Levi-Montalcini R, Angeletti PU (1968) Nerve growth factor. Physiol Rev 48(3):534–569PubMedGoogle Scholar
  129. Linggi MS, Burke TL, Williams BB, Harrington A, Kraemer R, Hempstead BL, Yoon SO, Carter BD (2005) Neurotrophin receptor interacting factor (NRIF) is an essential mediator of apoptotic signaling by the p75 neurotrophin receptor. J Biol Chem 280(14):13801–13808PubMedGoogle Scholar
  130. Mahadeo D, Kaplan L, Chao MV, Hempstead BL (1994) High affinity nerve growth factor binding displays a faster rate of association than p140trk binding. Implications for multi-subunit polypeptide receptors. J Biol Chem 269(9):6884–6891PubMedGoogle Scholar
  131. Maisonpierre PC, Belluscio L, Friedman B, Alderson RF, Wiegand SJ, Furth ME, Lindsay RM, Yancopoulos GD (1990a) NT-3, BDNF, and NGF in the developing rat nervous system: parallel as well as reciprocal patterns of expression. Neuron 5(4):501–509PubMedGoogle Scholar
  132. Maisonpierre PC, Belluscio L, Squinto S, Ip NY, Furth ME, Lindsay RM, Yancopoulos GD (1990b) Neurotrophin-3: a neurotrophic factor related to NGF and BDNF. Science 247(4949 Pt 1):1446–1451PubMedGoogle Scholar
  133. Majdan M, Walsh GS, Aloyz R, Miller FD (2001) TrkA mediates developmental sympathetic neuron survival in vivo by silencing an ongoing p75NTR-mediated death signal. J Cell Biol 155(7):1275–1285PubMedCentralPubMedGoogle Scholar
  134. Mamidipudi V, Li X, Wooten MW (2002) Identification of interleukin 1 receptor-associated kinase as a conserved component in the p75-neurotrophin receptor activation of nuclear factor-kappa B. J Biol Chem 277(31):28010–28018PubMedGoogle Scholar
  135. Mamidipudi V, Lin C, Seibenhener ML, Wooten MW (2004) Regulation of interleukin receptor-associated kinase (IRAK) phosphorylation and signaling by iota protein kinase C. J Biol Chem 279(6):4161–4165PubMedGoogle Scholar
  136. Massa SM, Xie Y, Yang T, Harrington AW, Kim ML, Yoon SO, Kraemer R, Moore LA, Hempstead BL, Longo FM (2006) Small, nonpeptide p75NTR ligands induce survival signaling and inhibit proNGF-induced death. J Neurosci 26(20):5288–5300PubMedGoogle Scholar
  137. Matrone C, Marolda R, Ciafre S, Ciotti MT, Mercanti D, Calissano P (2009) Tyrosine kinase nerve growth factor receptor switches from prosurvival to proapoptotic activity via Abeta-mediated phosphorylation. Proc Natl Acad Sci USA 106(27):11358–11363PubMedCentralPubMedGoogle Scholar
  138. Meakin SO, MacDonald JI, Gryz EA, Kubu CJ, Verdi JM (1999) The signaling adapter FRS-2 competes with Shc for binding to the nerve growth factor receptor TrkA. A model for discriminating proliferation and differentiation. J Biol Chem 274(14):9861–9870PubMedGoogle Scholar
  139. Minichiello L, Klein R (1996) TrkB and TrkC neurotrophin receptors cooperate in promoting survival of hippocampal and cerebellar granule neurons. Genes Dev 10(22):2849–2858PubMedGoogle Scholar
  140. Monteggia LM, Luikart B, Barrot M, Theobold D, Malkovska I, Nef S, Parada LF, Nestler EJ (2007) Brain-derived neurotrophic factor conditional knockouts show gender differences in depression-related behaviors. Biol Psychiatry 61(2):187–197PubMedGoogle Scholar
  141. Mukai J, Hachiya T, Shoji-Hoshino S, Kimura MT, Nadano D, Suvanto P, Hanaoka T, Li Y, Irie S, Greene LA, Sato TA (2000) NADE, a p75NTR-associated cell death executor, is involved in signal transduction mediated by the common neurotrophin receptor p75NTR. J Biol Chem 275(23):17566–17570PubMedGoogle Scholar
  142. Muragaki Y, Chou TT, Kaplan DR, Trojanowski JQ, Lee VM (1997) Nerve growth factor induces apoptosis in human medulloblastoma cell lines that express TrkA receptors. J Neurosci 17(2):530–542PubMedGoogle Scholar
  143. Murray SS, Bartlett PF, Cheema SS (1999) Differential loss of spinal sensory but not motor neurons in the p75NTR knockout mouse. Neurosci Lett 267(1):45–48PubMedGoogle Scholar
  144. Murray SS, Perez P, Lee R, Hempstead BL, Chao MV (2004) A novel p75 neurotrophin receptor-related protein, NRH2, regulates nerve growth factor binding to the TrkA receptor. J Neurosci 24(11):2742–2749PubMedGoogle Scholar
  145. Nikoletopoulou V, Lickert H, Frade JM, Rencurel C, Giallonardo P, Zhang L, Bibel M, Barde YA (2010) Neurotrophin receptors TrkA and TrkC cause neuronal death whereas TrkB does not. Nature 467(7311):59–63PubMedGoogle Scholar
  146. Nykjaer A, Willnow TE (2012) Sortilin: a receptor to regulate neuronal viability and function. Trends Neurosci 35(4):261–270PubMedGoogle Scholar
  147. O’Neill LA, Kaltschmidt C (1997) NF-kappa B: a crucial transcription factor for glial and neuronal cell function. Trends Neurosci 20(6):252–258PubMedGoogle Scholar
  148. Onishi-Haraikawa Y, Funaki M, Gotoh N, Shibuya M, Inukai K, Katagiri H, Fukushima Y, Anai M, Ogihara T, Sakoda H, Ono H, Kikuchi M, Oka Y, Asano T (2001) Unique phosphorylation mechanism of Gab1 using PI 3-kinase as an adaptor protein. Biochem Biophys Res Commun 288(2):476–482PubMedGoogle Scholar
  149. Oppenheim RW (1991) Cell death during development of the nervous system. Annu Rev Neurosci 14:453–501PubMedGoogle Scholar
  150. Ozes ON, Mayo LD, Gustin JA, Pfeffer SR, Pfeffer LM, Donner DB (1999) NF-kappaB activation by tumour necrosis factor requires the Akt serine-threonine kinase. Nature 401(6748):82–85PubMedGoogle Scholar
  151. Park JA, Lee JY, Sato TA, Koh JY (2000) Co-induction of p75NTR and p75NTR-associated death executor in neurons after zinc exposure in cortical culture or transient ischemia in the rat. J Neurosci 20(24):9096–9103PubMedGoogle Scholar
  152. Park HH, Lo YC, Lin SC, Wang L, Yang JK, Wu H (2007) The death domain superfamily in intracellular signaling of apoptosis and inflammation. Annu Rev Immunol 25:561–586PubMedCentralPubMedGoogle Scholar
  153. Pazyra-Murphy MF, Hans A, Courchesne SL, Karch C, Cosker KE, Heerssen HM, Watson FL, Kim T, Greenberg ME, Segal RA (2009) A retrograde neuronal survival response: target-derived neurotrophins regulate MEF2D and bcl-w. J Neurosci 29(20):6700–6709PubMedCentralPubMedGoogle Scholar
  154. Provenzano MJ, Xu N, Ver Meer MR, Clark JJ, Hansen MR (2008) p75NTR and sortilin increase after facial nerve injury. Laryngoscope 118(1):87–93PubMedGoogle Scholar
  155. Rauskolb S, Zagrebelsky M, Dreznjak A, Deogracias R, Matsumoto T, Wiese S, Erne B, Sendtner M, Schaeren-Wiemers N, Korte M, Barde YA (2010) Global deprivation of brain-derived neurotrophic factor in the CNS reveals an area-specific requirement for dendritic growth. J Neurosci 30(5):1739–1749PubMedGoogle Scholar
  156. Riccio A, Pierchala BA, Ciarallo CL, Ginty DD (1997) An NGF-TrkA-mediated retrograde signal to transcription factor CREB in sympathetic neurons. Science 277(5329):1097–1100PubMedGoogle Scholar
  157. Rios M, Fan G, Fekete C, Kelly J, Bates B, Kuehn R, Lechan RM, Jaenisch R (2001) Conditional deletion of brain-derived neurotrophic factor in the postnatal brain leads to obesity and hyperactivity. Mol Endocrinol 15(10):1748–1757PubMedGoogle Scholar
  158. Rodriguez-Tebar A, Dechant G, Barde YA (1990) Binding of brain-derived neurotrophic factor to the nerve growth factor receptor. Neuron 4(4):487–492PubMedGoogle Scholar
  159. Rodriguez-Tebar A, Dechant G, Gotz R, Barde YA (1992) Binding of neurotrophin-3 to its neuronal receptors and interactions with nerve growth factor and brain-derived neurotrophic factor. EMBO J 11(3):917–922PubMedCentralPubMedGoogle Scholar
  160. Romashkova JA, Makarov SS (1999) NF-kappaB is a target of AKT in anti-apoptotic PDGF signalling. Nature 401(6748):86–90PubMedGoogle Scholar
  161. Roux PP, Colicos MA, Barker PA, Kennedy TE (1999) p75 neurotrophin receptor expression is induced in apoptotic neurons after seizure. J Neurosci 19(16):6887–6896PubMedGoogle Scholar
  162. Roux PP, Bhakar AL, Kennedy TE, Barker PA (2001) The p75 neurotrophin receptor activates Akt (protein kinase B) through a phosphatidylinositol 3-kinase-dependent pathway. J Biol Chem 276(25):23097–23104PubMedGoogle Scholar
  163. Ryden M, Hempstead B, Ibanez CF (1997) Differential modulation of neuron survival during development by nerve growth factor binding to the p75 neurotrophin receptor. J Biol Chem 272(26):16322–16328PubMedGoogle Scholar
  164. Salehi AH, Roux PP, Kubu CJ, Zeindler C, Bhakar A, Tannis LL, Verdi JM, Barker PA (2000) NRAGE, a novel MAGE protein, interacts with the p75 neurotrophin receptor and facilitates nerve growth factor-dependent apoptosis. Neuron 27(2):279–288PubMedGoogle Scholar
  165. Salehi AH, Xanthoudakis S, Barker PA (2002) NRAGE, a p75 neurotrophin receptor-interacting protein, induces caspase activation and cell death through a JNK-dependent mitochondrial pathway. J Biol Chem 277(50):48043–48050PubMedGoogle Scholar
  166. Sedel F, Bechade C, Triller A (1999) Nerve growth factor (NGF) induces motoneuron apoptosis in rat embryonic spinal cord in vitro. Eur J Neurosci 11(11):3904–3912PubMedGoogle Scholar
  167. Segal RA, Goumnerova LC, Kwon YK, Stiles CD, Pomeroy SL (1994) Expression of the neurotrophin receptor TrkC is linked to a favorable outcome in medulloblastoma. Proc Natl Acad Sci USA 91(26):12867–12871PubMedCentralPubMedGoogle Scholar
  168. Sendtner M, Holtmann B, Hughes RA (1996) The response of motoneurons to neurotrophins. Neurochem Res 21(7):831–841PubMedGoogle Scholar
  169. Shi Z, Birman E, Saragovi HU (2007) Neurotrophic rationale in glaucoma: a TrkA agonist, but not NGF or a p75 antagonist, protects retinal ganglion cells in vivo. Dev Neurobiol 67(7):884–894PubMedGoogle Scholar
  170. Skaper SD (2008) The biology of neurotrophins, signalling pathways, and functional peptide mimetics of neurotrophins and their receptors. CNS Neurol Disord Drug Targets 7(1):46–62PubMedGoogle Scholar
  171. Smeyne RJ, Klein R, Schnapp A, Long LK, Bryant S, Lewin A, Lira SA, Barbacid M (1994) Severe sensory and sympathetic neuropathies in mice carrying a disrupted Trk/NGF receptor gene. Nature 368(6468):246–249PubMedGoogle Scholar
  172. Song W, Volosin M, Cragnolini AB, Hempstead BL, Friedman WJ (2010) ProNGF induces PTEN via p75NTR to suppress Trk-mediated survival signaling in brain neurons. J Neurosci 30(46):15608–15615PubMedCentralPubMedGoogle Scholar
  173. Squinto SP, Stitt TN, Aldrich TH, Davis S, Bianco SM, Radziejewski C, Glass DJ, Masiakowski P, Furth ME, Valenzuela DM et al (1991) trkB encodes a functional receptor for brain-derived neurotrophic factor and neurotrophin-3 but not nerve growth factor. Cell 65(5):885–893PubMedGoogle Scholar
  174. Stucky CL, Shin JB, Lewin GR (2002) Neurotrophin-4: a survival factor for adult sensory neurons. Curr Biol 12(16):1401–1404PubMedGoogle Scholar
  175. Sutter A, Riopelle RJ, Harris-Warrick RM, Shooter EM (1979) Nerve growth factor receptors. Characterization of two distinct classes of binding sites on chick embryo sensory ganglia cells. J Biol Chem 254(13):5972–5982PubMedGoogle Scholar
  176. Syroid DE, Maycox PJ, Soilu-Hanninen M, Petratos S, Bucci T, Burrola P, Murray S, Cheema S, Lee KF, Lemke G, Kilpatrick TJ (2000) Induction of postnatal schwann cell death by the low-affinity neurotrophin receptor in vitro and after axotomy. J Neurosci 20(15):5741–5747PubMedGoogle Scholar
  177. Tauszig-Delamasure S, Yu LY, Cabrera JR, Bouzas-Rodriguez J, Mermet-Bouvier C, Guix C, Bordeaux MC, Arumae U, Mehlen P (2007) The TrkC receptor induces apoptosis when the dependence receptor notion meets the neurotrophin paradigm. Proc Natl Acad Sci USA 104(33):13361–13366PubMedCentralPubMedGoogle Scholar
  178. Troy CM, Friedman JE, Friedman WJ (2002) Mechanisms of p75-mediated death of hippocampal neurons. Role of caspases. J Biol Chem 277(37):34295–34302PubMedGoogle Scholar
  179. Twiss JL, Wada HG, Fok KS, Chan SD, Verity AN, Baxter GT, Shooter EM, Sussman HH (1998) Duration and magnitude of nerve growth factor signaling depend on the ratio of p75LNTR to TrkA. J Neurosci Res 51(4):442–453PubMedGoogle Scholar
  180. Vaegter CB, Jansen P, Fjorback AW, Glerup S, Skeldal S, Kjolby M, Richner M, Erdmann B, Nyengaard JR, Tessarollo L, Lewin GR, Willnow TE, Chao MV, Nykjaer A (2011) Sortilin associates with Trk receptors to enhance anterograde transport and neurotrophin signaling. Nat Neurosci 14(1):54–61PubMedGoogle Scholar
  181. Valdes-Sanchez T, Kirstein M, Perez-Villalba A, Vega JA, Farinas I (2010) BDNF is essentially required for the early postnatal survival of nociceptors. Dev Biol 339(2):465–476PubMedGoogle Scholar
  182. Van der Zee CE, Ross GM, Riopelle RJ, Hagg T (1996) Survival of cholinergic forebrain neurons in developing p75NGFR-deficient mice. Science 274(5293):1729–1732PubMedGoogle Scholar
  183. Varsano T, Dong MQ, Niesman I, Gacula H, Lou X, Ma T, Testa JR, Yates JR 3rd, Farquhar MG (2006) GIPC is recruited by APPL to peripheral TrkA endosomes and regulates TrkA trafficking and signaling. Mol Cell Biol 26(23):8942–8952PubMedCentralPubMedGoogle Scholar
  184. Verdi JM, Birren SJ, Ibanez CF, Persson H, Kaplan DR, Benedetti M, Chao MV, Anderson DJ (1994) p75LNGFR regulates Trk signal transduction and NGF-induced neuronal differentiation in MAH cells. Neuron 12(4):733–745PubMedGoogle Scholar
  185. Volosin M, Song W, Almeida RD, Kaplan DR, Hempstead BL, Friedman WJ (2006) Interaction of survival and death signaling in basal forebrain neurons: roles of neurotrophins and proneurotrophins. J Neurosci 26(29):7756–7766PubMedGoogle Scholar
  186. von Schack D, Casademunt E, Schweigreiter R, Meyer M, Bibel M, Dechant G (2001) Complete ablation of the neurotrophin receptor p75NTR causes defects both in the nervous and the vascular system. Nat Neurosci 4(10):977–978Google Scholar
  187. Wang L, Yang JK, Kabaleeswaran V, Rice AJ, Cruz AC, Park AY, Yin Q, Damko E, Jang SB, Raunser S, Robinson CV, Siegel RM, Walz T, Wu H (2010) The Fas-FADD death domain complex structure reveals the basis of DISC assembly and disease mutations. Nat Struct Mol Biol 17(11):1324–1329PubMedCentralPubMedGoogle Scholar
  188. Watson FL, Heerssen HM, Bhattacharyya A, Klesse L, Lin MZ, Segal RA (2001) Neurotrophins use the Erk5 pathway to mediate a retrograde survival response. Nat Neurosci 4(10):981–988PubMedGoogle Scholar
  189. Wehrman T, He X, Raab B, Dukipatti A, Blau H, Garcia KC (2007) Structural and mechanistic insights into nerve growth factor interactions with the TrkA and p75 receptors. Neuron 53(1):25–38PubMedGoogle Scholar
  190. White FA, Silos-Santiago I, Molliver DC, Nishimura M, Phillips H, Barbacid M, Snider WD (1996) Synchronous onset of NGF and TrkA survival dependence in developing dorsal root ganglia. J Neurosci 16(15):4662–4672PubMedGoogle Scholar
  191. Willard MD, Willard FS, Li X, Cappell SD, Snider WD, Siderovski DP (2007) Selective role for RGS12 as a Ras/Raf/MEK scaffold in nerve growth factor-mediated differentiation. EMBO J 26(8):2029–2040PubMedCentralPubMedGoogle Scholar
  192. Wilson KH (2009) The genome sequence of the protostome Daphnia pulex encodes respective orthologues of a neurotrophin, a Trk and a p75NTR: evolution of neurotrophin signaling components and related proteins in the bilateria. BMC Evol Biol 9:243PubMedCentralPubMedGoogle Scholar
  193. Wong AW, Willingham M, Xiao J, Kilpatrick TJ, Murray SS (2008) Neurotrophin receptor homolog-2 regulates nerve growth factor signaling. J Neurochem 106(4):1964–1976PubMedGoogle Scholar
  194. Xu B, Zang K, Ruff NL, Zhang YA, McConnell SK, Stryker MP, Reichardt LF (2000) Cortical degeneration in the absence of neurotrophin signaling: dendritic retraction and neuronal loss after removal of the receptor TrkB. Neuron 26(1):233–245PubMedGoogle Scholar
  195. Yan H, Schlessinger J, Chao MV (1991) Chimeric NGF-EGF receptors define domains responsible for neuronal differentiation. Science 252(5005):561–563PubMedGoogle Scholar
  196. Yano H, Lee FS, Kong H, Chuang J, Arevalo J, Perez P, Sung C, Chao MV (2001) Association of Trk neurotrophin receptors with components of the cytoplasmic dynein motor. J Neurosci 21(3):RC125Google Scholar
  197. Yeiser EC, Rutkoski NJ, Naito A, Inoue J, Carter BD (2004) Neurotrophin signaling through the p75 receptor is deficient in traf6−/− mice. J Neurosci 24(46):10521–10529PubMedGoogle Scholar
  198. Yeo TT, Chua-Couzens J, Butcher LL, Bredesen DE, Cooper JD, Valletta JS, Mobley WC, Longo FM (1997) Absence of p75NTR causes increased basal forebrain cholinergic neuron size, choline acetyltransferase activity, and target innervation. J Neurosci 17(20):7594–7605PubMedGoogle Scholar
  199. York RD, Molliver DC, Grewal SS, Stenberg PE, McCleskey EW, Stork PJ (2000) Role of phosphoinositide 3-kinase and endocytosis in nerve growth factor-induced extracellular signal-regulated kinase activation via Ras and Rap1. Mol Cell Biol 20(21):8069–8083PubMedCentralPubMedGoogle Scholar
  200. Young KM, Merson TD, Sotthibundhu A, Coulson EJ, Bartlett PF (2007) p75 neurotrophin receptor expression defines a population of BDNF-responsive neurogenic precursor cells. J Neurosci 27(19):5146–5155PubMedGoogle Scholar
  201. Yune TY, Lee JY, Jung GY, Kim SJ, Jiang MH, Kim YC, Oh YJ, Markelonis GJ, Oh TH (2007) Minocycline alleviates death of oligodendrocytes by inhibiting pro-nerve growth factor production in microglia after spinal cord injury. J Neurosci 27(29):7751–7761PubMedGoogle Scholar
  202. Zafra F, Lindholm D, Castren E, Hartikka J, Thoenen H (1992) Regulation of brain-derived neurotrophic factor and nerve growth factor mRNA in primary cultures of hippocampal neurons and astrocytes. J Neurosci 12(12):4793–4799PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014 2014

Authors and Affiliations

  • Claire Ceni
    • 1
  • Nicolas Unsain
    • 1
  • Michele P. Zeinieh
    • 1
  • Philip A. Barker
    • 1
  1. 1.Centre for Neuronal SurvivalMontreal Neurological Institute, McGill UniversityMontrealCanada

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