Advertisement

nPKCε Mediates SNAP-25 Phosphorylation of Ser-187 in Basal Conditions and After Synaptic Activity at the Neuromuscular Junction

  • Anna Simó
  • Victor Cilleros-Mañé
  • Laia Just-Borràs
  • Erica Hurtado
  • Laura Nadal
  • Marta Tomàs
  • Neus Garcia
  • Maria A. LanuzaEmail author
  • Josep TomàsEmail author
Article
  • 50 Downloads

Abstract

Protein kinase C (PKC) and substrates like SNAP-25 regulate neurotransmission. At the neuromuscular junction (NMJ), PKC promotes neurotransmitter release during synaptic activity. Thirty minutes of muscle contraction enhances presynaptic PKC isoform levels, specifically cPKCβI and nPKCε, through retrograde BDNF/TrkB signaling. This establishes a larger pool of these PKC isoforms ready to promote neuromuscular transmission. The PKC phosphorylation site in SNAP-25 has been mapped to the serine 187 (Ser-187), which is known to enhance calcium-dependent neurotransmitter release in vitro. Here, we localize SNAP-25 at the NMJ and investigate whether cPKCβI and/or nPKCε regulate SNAP-25 phosphorylation. We also investigate whether nerve and muscle cell activities regulate differently SNAP-25 phosphorylation and the involvement of BDNF/TrkB signaling. Our results demonstrate that nPKCε isoform is essential to positively regulate SNAP-25 phosphorylation on Ser-187 and that muscle contraction prevents it. TrkB and cPKCβI do not regulate SNAP-25 protein level or its phosphorylation during neuromuscular activity. The results provide evidence that nerve terminals need both pre- and postsynaptic activities to modulate SNAP-25 phosphorylation and ensure an accurate neurotransmission process.

Keywords

Neuromuscular junction Muscle contraction SNAP-25 TrkB PKC Neurotransmission Synaptic vesicles 

Abbreviations

47/TrkB

Anti-TrkB antibody clone 47/TrkB

ACh

Acetylcholine

AChR

Acetylcholine receptor

BDNF

Brain-derived neurotrophic factor

Ca2+

Calcium ion

CNS

Central nervous system

cPKCβI

Conventional protein kinase C beta I

ECL

Enhanced chemiluminescence

GAPDH

Glyceraldehyde-3-phosphate dehydrogenase

HRP

Horseradish peroxidase

LAL

Levator auris longus

NMJ

Neuromuscular junction

nPKCε

Novel protein kinase C epsilon

NT-4/5

Neurotrophin-4/5

p75

p75 neurotrophin receptor

PBS

Phosphate buffer saline

PKC

Protein kinase C

PLC

Phospholipase C

PMA

Phorbol 12-myristate 13-acetate

pSNAP-25

Phosphorylated synaptosomal-associated protein of 25 kDa

PVDF

Polyvinylidene difluoride

RACK

Receptor for activated C-kinase

SDS

Sodium dodecyl sulfate

Ser-187

Serine 187

SNAP-25

Synaptosomal-associated protein of 25 kDa

SNARE

Soluble N-ethylmaleimide-sensitive factor attachment receptor proteins

TrkA

Tropomyosin receptor kinase A

TrkB

Tropomyosin receptor kinase B

TrkC

Tropomyosin receptor kinase C

α-BTX

α-Bungarotoxin

βIV5-3

cPKCβI-specific translocation inhibitor peptide

εV1-2

nPKCε-specific translocation inhibitor peptide

μ-CgTx-GIIIB

μ-Conotoxin GIIIB

VGCC

Voltage-gated calcium channels

Notes

Acknowledgments

We would like to thank Dr. Daria Mochly-Rosen and Dr. Nir Qvit for providing the specific translocation inhibitor peptide of cPKCβI (βIV5-3).

Authors’ Contributions

A.S.: data collection, quantitative analysis, literature search, data interpretation, statistics; V.C., L.J.: data collection, quantitative analyses, literature search, data interpretation, design graphic abstract; E.H., L.N., and M.T.: data interpretation; J.T., M.A.L, and N.G.: conception and design, literature search, data interpretation, manuscript preparation

Funding Information

This work has been possible with the support of the Ministerio de Economía, Industria y Competitividad (MINECO), the Agencia Estatal de Investigación (AEI), the European Regional Development Fund (ERDF) (SAF2015-67143-P), the Universitat Rovira i Virgili (URV) (2014PFR-URV-B2-83 and 2017PFR-URV-B2-85), and the Catalan Government (2014SGR344 and 2017SGR704). V.C. has been supported by MINECO under the framework of the Sistema Nacional de Garantía Juvenil, the European Social Fund (ESF), and the Iniciativa de Empleo Juvenil (IEJ).

Compliance with Ethical Standards

Young adult Sprague-Dawley rats (30–40 days; Criffa, Barcelona, Spain; RRID:RGD_5508397) were cared for in accordance with the guidelines of the European Community Council Directive for the humane treatment of laboratory animals. All the procedures were approved by the Animal Experimentation Ethics Committee of the Universitat Rovira i Virgili.

Competing Interests

The authors declare that they have no competing interests.

References

  1. 1.
    Byrne JH, Kandel ER (1996) Presynaptic facilitation revisited: state and time dependence. J Neurosci 16:425–435.  https://doi.org/10.1523/JNEUROSCI.16-02-00425 CrossRefPubMedGoogle Scholar
  2. 2.
    Numann R, Hauschka SD, Catterall WA, Scheuer T (1994) Modulation of skeletal muscle sodium channels in a satellite cell line by protein kinase C. J Neurosci 14:4226–4236.  https://doi.org/10.1523/JNEUROSCI.14-07-04226 CrossRefPubMedGoogle Scholar
  3. 3.
    Santafé MM, Lanuza MA, Garcia N, Tomàs J (2005) Calcium inflow-dependent protein kinase C activity is involved in the modulation of transmitter release in the neuromuscular junction of the adult rat. Synapse 57:76–84.  https://doi.org/10.1002/syn.20159 CrossRefPubMedGoogle Scholar
  4. 4.
    Santafé MM, Lanuza MA, Garcia N, Tomàs J (2006) Muscarinic autoreceptors modulate transmitter release through protein kinase C and protein kinase A in the rat motor nerve terminal. Eur J Neurosci 23:2048–2056.  https://doi.org/10.1111/j.1460-9568.2006.04753.x CrossRefPubMedGoogle Scholar
  5. 5.
    Tomàs J, Santafé MM, Garcia N, Lanuza MA, Tomàs M, Besalduch N, Obis T, Priego M et al (2014) Presynaptic membrane receptors in acetylcholine release modulation in the neuromuscular synapse. J Neurosci Res 92:543–554.  https://doi.org/10.1002/jnr.23346 CrossRefPubMedGoogle Scholar
  6. 6.
    West J, Numann R, Murphy B et al (1991) Identification of an intracellular peptide segment involved in sodium channel inactivation. Science (80- ) 241:1658–1661.  https://doi.org/10.1126/science.2458625 CrossRefGoogle Scholar
  7. 7.
    Catterall WA (1999) Interactions of presynaptic Ca2+ channels and Snare proteins in neurotransmitter release. Ann N Y Acad Sci 868:144–159.  https://doi.org/10.1111/j.1749-6632.1999.tb11284.x CrossRefPubMedGoogle Scholar
  8. 8.
    Snyder DA, Kelly ML, Woodbury DJ (2006) SNARE complex regulation by phosphorylation. Cell Biochem Biophys 45:111–123.  https://doi.org/10.1385/CBB:45:1:111 CrossRefPubMedGoogle Scholar
  9. 9.
    Shimazaki Y, Nishiki T, Omori A, Sekiguchi M, Kamata Y, Kozaki S, Takahashi M (1996) Phosphorylation of 25-kDa synaptosome-associated protein. Possible involvement in protein kinase C-mediated regulation of neurotransmitter release. J Biol Chem 271:14548–14553.  https://doi.org/10.1074/JBC.271.24.14548 CrossRefPubMedGoogle Scholar
  10. 10.
    Kataoka M, Kuwahara R, Iwasaki S, Shoji-Kasai Y, Takahashi M (2000) Nerve growth factor-induced phosphorylation of SNAP-25 in PC12 cells. J Neurochem 74:2058–2066.  https://doi.org/10.1046/j.1471-4159.2000.0742058.x CrossRefPubMedGoogle Scholar
  11. 11.
    Söllner T, Whiteheart SW, Brunner M, Erdjument-Bromage H, Geromanos S, Tempst P, Rothman JE (1993) SNAP receptors implicated in vesicle targeting and fusion. Nature 362:318–324.  https://doi.org/10.1038/362318a0 CrossRefPubMedGoogle Scholar
  12. 12.
    Mohrmann R, de Wit H, Verhage M, Neher E, Sorensen JB (2010) Fast vesicle fusion in living cells requires at least three SNARE complexes. Science 330:502–505.  https://doi.org/10.1126/science.1193134 CrossRefPubMedGoogle Scholar
  13. 13.
    Morgan A, Burgoyne RD, Barclay JW, Craig TJ, Prescott GR, Ciufo LF, Evans GJO, Graham ME (2005) Regulation of exocytosis by protein kinase C. Biochem Soc Trans 33:1341–1344.  https://doi.org/10.1042/BST20051341 CrossRefPubMedGoogle Scholar
  14. 14.
    Yang Y, Craig TJ, Chen X, Ciufo LF, Takahashi M, Morgan A, Gillis KD (2007) Phosphomimetic mutation of Ser-187 of SNAP-25 increases both syntaxin binding and highly Ca2+-sensitive exocytosis. J Gen Physiol 129:233–244.  https://doi.org/10.1085/jgp.200609685 CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Katayama N, Yamamori S, Fukaya M, Kobayashi S, Watanabe M, Takahashi M, Manabe T (2017) SNAP-25 phosphorylation at Ser187 regulates synaptic facilitation and short-term plasticity in an age-dependent manner. Sci Rep 7:7996.  https://doi.org/10.1038/s41598-017-08237-x CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Nagy G, Matti U, Nehring RB, Binz T, Rettig J, Neher E, Sørensen JB (2002) Protein kinase C-dependent phosphorylation of synaptosome-associated protein of 25 kDa at Ser187 potentiates vesicle recruitment. J Neurosci 22:9278–9286.  https://doi.org/10.1523/JNEUROSCI.22-21-09278.2002 CrossRefPubMedGoogle Scholar
  17. 17.
    Leenders AGM, Sheng Z-H (2005) Modulation of neurotransmitter release by the second messenger-activated protein kinases: implications for presynaptic plasticity. Pharmacol Ther 105:69–84.  https://doi.org/10.1016/j.pharmthera.2004.10.012 CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Sørensen JB, Nagy G, Varoqueaux F, Nehring RB, Brose N, Wilson MC, Neher E (2003) Differential control of the releasable vesicle pools by SNAP-25 splice variants and SNAP-23. Cell 114:75–86.  https://doi.org/10.1016/S0092-8674(03)00477-X CrossRefPubMedGoogle Scholar
  19. 19.
    Sørensen JB, Matti U, Wei S-H et al (2002) The SNARE protein SNAP-25 is linked to fast calcium triggering of exocytosis. Proc Natl Acad Sci U S A 99:1627–1632.  https://doi.org/10.1073/pnas.251673298 CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Zhang Z, Wang D, Sun T, Xu J, Chiang HC, Shin W, Wu LG (2013) The SNARE proteins SNAP25 and synaptobrevin are involved in endocytosis at hippocampal synapses. J Neurosci 33:9169–9175.  https://doi.org/10.1523/JNEUROSCI.0301-13.2013 CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Pozzi D, Condliffe S, Bozzi Y, Chikhladze M, Grumelli C, Proux-Gillardeaux V, Takahashi M, Franceschetti S et al (2008) Activity-dependent phosphorylation of Ser187 is required for SNAP-25-negative modulation of neuronal voltage-gated calcium channels. Proc Natl Acad Sci U S A 105:323–328.  https://doi.org/10.1073/pnas.0706211105 CrossRefPubMedGoogle Scholar
  22. 22.
    Verderio C, Pozzi D, Pravettoni E, Inverardi F, Schenk U, Coco S, Proux-Gillardeaux V, Galli T et al (2004) SNAP-25 modulation of calcium dynamics underlies differences in GABAergic and glutamatergic responsiveness to depolarization. Neuron 41:599–610.  https://doi.org/10.1016/S0896-6273(04)00077-7 CrossRefPubMedGoogle Scholar
  23. 23.
    Besalduch N, Tomàs M, Santafé MM et al (2010) Synaptic activity-related classical protein kinase C isoform localization in the adult rat neuromuscular synapse. J Comp Neurol 518:211–228.  https://doi.org/10.1002/cne.22220 CrossRefPubMedGoogle Scholar
  24. 24.
    Hurtado E, Cilleros V, Nadal L et al (2017) Muscle contraction regulates BDNF/TrkB signaling to modulate synaptic function through presynaptic cPKCα and cPKCβI. Front Mol Neurosci 10:1–22.  https://doi.org/10.3389/fnmol2017.00147 CrossRefGoogle Scholar
  25. 25.
    Obis T, Hurtado E, Nadal L, Tomàs M, Priego M, Simon A, Garcia N, Santafe MM et al (2015) The novel protein kinase C epsilon isoform modulates acetylcholine release in the rat neuromuscular junction. Mol Brain 8:80.  https://doi.org/10.1186/s13041-015-0171-5 CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Obis T, Besalduch N, Hurtado E, Nadal L, Santafe MM, Garcia N, Tomàs M, Priego M et al (2015) The novel protein kinase C epsilon isoform at the adult neuromuscular synapse: location, regulation by synaptic activity-dependent muscle contraction through TrkB signaling and coupling to ACh release. Mol Brain 8:8.  https://doi.org/10.1186/s13041-015-0098-x CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Ravichandran V, Chawla A, Roche PA (1996) Identification of a novel syntaxin- and synaptobrevin/VAMP-binding protein, SNAP-23, expressed in non-neuronal tissues. J Biol Chem 271:13300–13303.  https://doi.org/10.1074/JBC.271.23.13300 CrossRefPubMedGoogle Scholar
  28. 28.
    Yu Y, Fuscoe JC, Zhao C, Guo C, Jia M, Qing T, Bannon DI, Lancashire L et al (2014) A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages. Nat Commun 5:3230.  https://doi.org/10.1038/ncomms4230 CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Boström P, Andersson L, Vind B, Håversen L, Rutberg M, Wickström Y, Larsson E, Jansson PA et al (2010) The SNARE protein SNAP23 and the SNARE-interacting protein Munc18c in human skeletal muscle are implicated in insulin resistance/type 2 diabetes. Diabetes 59:1870–1878.  https://doi.org/10.2337/db09-1503 CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Rapaport D, Lugassy Y, Sprecher E, Horowitz M (2010) Loss of SNAP29 impairs endocytic recycling and cell motility. PLoS One 5:e9759.  https://doi.org/10.1371/journal.pone.0009759 CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Iwasaki S, Kataoka M, Sekiguchi M, Shimazaki Y, Sato K, Takahasi M (2000) Two distinct mechanisms underlie the stimulation of neurotransmitter release by phorbol esters in clonal rat pheochromocytoma PC12 cells. J Biochem 128:407–414CrossRefGoogle Scholar
  32. 32.
    Wierda KDB, Toonen RFG, de Wit H, Brussaard AB, Verhage M (2007) Interdependence of PKC-dependent and PKC-independent pathways for presynaptic plasticity. Neuron 54:275–290.  https://doi.org/10.1016/j.neuron.2007.04.001 CrossRefPubMedGoogle Scholar
  33. 33.
    Losavio A, Muchnik S (2000) Facilitation of spontaneous acetylcholine release induced by activation of cAMP in rat neuromuscular junctions. Life Sci 66:2543–2556.  https://doi.org/10.1016/S0024-3205(00)00588-9 CrossRefPubMedGoogle Scholar
  34. 34.
    Liu GS, Cohen MV, Mochly-Rosen D, Downey JM (1999) Protein kinase C- ξ is responsible for the protection of preconditioning in rabbit cardiomyocytes. J Mol Cell Cardiol 31:1937–1948.  https://doi.org/10.1006/jmcc.1999.1026 CrossRefPubMedGoogle Scholar
  35. 35.
    Zhang Y, Ying J, Jiang D, Chang Z, Li H, Zhang G, Gong S, Jiang X et al (2015) Urotensin-II receptor stimulation of cardiac L-type Ca2+ channels requires the βγ subunits of Gi/o-protein and phosphatidylinositol 3-kinase-dependent protein kinase C β1 isoform. J Biol Chem 290:8644–8655.  https://doi.org/10.1074/jbc.M114.615021 CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Johnson JA, Gray MO, Chen CH, Mochly-Rosen D (1996) A protein kinase C translocation inhibitor as an isozyme-selective antagonist of cardiac function. J Biol Chem 271:24962–24966.  https://doi.org/10.1074/JBC.271.40.24962 CrossRefPubMedGoogle Scholar
  37. 37.
    Stebbins EG, Mochly-Rosen D (2001) Binding specificity for RACK1 resides in the V5 region of beta II protein kinase C. J Biol Chem 276:29644–29650.  https://doi.org/10.1074/jbc.M101044200 CrossRefPubMedGoogle Scholar
  38. 38.
    Stebbins EG, Mochly-Rosen D (2001) Binding specificity for RACK1 resides in the V5 region of βII protein kinase C. J Biol Chem 276:29644–29650.  https://doi.org/10.1074/jbc.M101044200 CrossRefPubMedGoogle Scholar
  39. 39.
    Mochly-Rosen D, Gordon AS (1998) Anchoring proteins for protein kinase C: a means for isozyme selectivity. FASEB J 12:35–42.  https://doi.org/10.1096/fasebj.12.1.35 CrossRefPubMedGoogle Scholar
  40. 40.
    Way KJ, Chou E, King GL (2000) Identification of PKC-isoform-specific biological actions using pharmacological approaches. Trends Pharmacol Sci 21:181–187.  https://doi.org/10.1016/S0165-6147(00)01468-1 CrossRefPubMedGoogle Scholar
  41. 41.
    Di-Capua N, Sperling O, Zoref-Shani E (2003) Protein kinase C-ε is involved in the adenosine-activated signal transduction pathway conferring protection against ischemia-reperfusion injury in primary rat neuronal cultures. J Neurochem 84:409–412.  https://doi.org/10.1046/j.1471-4159.2003.01563.x CrossRefPubMedGoogle Scholar
  42. 42.
    Khasar SG, Lin YH, Martin A, Dadgar J, McMahon T, Wang D, Hundle B, Aley KO et al (1999) A novel nociceptor signaling pathway revealed in protein kinase C epsilon mutant mice. Neuron 24:253–260.  https://doi.org/10.1016/S0896-6273(00)80837-5 CrossRefPubMedGoogle Scholar
  43. 43.
    Simó A, Just-Borràs L, Cilleros-Mañé V, Hurtado E, Nadal L, Tomàs M, Garcia N, Lanuza MA et al (2018) BDNF-TrkB signaling coupled to nPKCε and cPKCβI modulate the phosphorylation of the exocytotic protein Munc18-1 during synaptic activity at the neuromuscular junction. Front Mol Neurosci 11:207.  https://doi.org/10.3389/fnmol.2018.00207 CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Cazorla M, Prémont J, Mann A, Girard N, Kellendonk C, Rognan D (2011) Identification of a low–molecular weight TrkB antagonist with anxiolytic and antidepressant activity in mice. J Clin Invest 121:1846–1857.  https://doi.org/10.1172/JCI43992 CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Favreau P, Le Gall F, Benoit E, Molgó J (1999) A review on conotoxins targeting ion channels and acetylcholine receptors of the vertebrate neuromuscular junction. Acta Physiol Pharmacol Ther Latinoam 49:257–267PubMedGoogle Scholar
  46. 46.
    Santafé MM, Garcia N, Lanuza MA, Tomàs M, Tomàs J (2009) Interaction between protein kinase C and protein kinase A can modulate transmitter release at the rat neuromuscular synapse. J Neurosci Res 87:683–690.  https://doi.org/10.1002/jnr.21885 CrossRefPubMedGoogle Scholar
  47. 47.
    Lau CG, Takayasu Y, Rodenas-Ruano A, Paternain AV, Lerma J, Bennett MVL, Zukin RS (2010) SNAP-25 is a target of protein kinase C phosphorylation critical to NMDA receptor trafficking. J Neurosci 30:242–254.  https://doi.org/10.1523/JNEUROSCI.4933-08.2010 CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Zhang ZH, Johnson JA, Chen L, el-Sherif N, Mochly-Rosen D, Boutjdir M (1997) C2 region-derived peptides of beta-protein kinase C regulate cardiac Ca2+ channels. Circ Res 80:720–729.  https://doi.org/10.1161/res.80.5.720 CrossRefPubMedGoogle Scholar
  49. 49.
    Parker PJ, Bosca L, Dekker L, Goode NT, Hajibagheri N, Hansra G (1995) Protein kinase C (PKC)-induced PKC degradation: a model for down-regulation. Biochem Soc Trans 23:153–155.  https://doi.org/10.1042/BST0230153 CrossRefPubMedGoogle Scholar
  50. 50.
    Lu Z, Liu D, Hornia A, Devonish W, Pagano M, Foster DA (1998) Activation of protein kinase C triggers its ubiquitination and degradation. Mol Cell Biol 18:839–845.  https://doi.org/10.1128/MCB.18.2.839 CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Lehel C, Oláh Z, Jakab G, Szállási Z, Petrovics G, Harta G, Blumberg PM, Anderson WB (1995) Protein kinase C epsilon subcellular localization domains and proteolytic degradation sites. A model for protein kinase C conformational changes. J Biol Chem 270:19651–19658.  https://doi.org/10.1074/JBC.270.33.19651 CrossRefPubMedGoogle Scholar
  52. 52.
    Olivier AR, Parker PJ (1994) Bombesin, platelet-derived growth factor, and diacylglycerol induce selective membrane association and down-regulation of protein kinase C isotypes in Swiss 3T3 cells. J Biol Chem 269:2758–2763PubMedGoogle Scholar
  53. 53.
    Gould C, Newton A (2008) The life and death of protein kinase C. Curr Drug Targets 9:614–625.  https://doi.org/10.2174/138945008785132411 CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Balkowiec A, Katz DM (2000) Activity-dependent release of endogenous brain-derived neurotrophic factor from primary sensory neurons detected by ELISA in situ. J Neurosci 20:7417–7423.  https://doi.org/10.1523/JNEUROSCI.20-19-07417.2000 CrossRefPubMedGoogle Scholar
  55. 55.
    Oyler GA, Polli JW, Higgins GA, Wilson MC, Billingsley ML (1992) Distribution and expression of SNAP-25 immunoreactivity in rat brain, rat PC-12 cells and human SMS-KCNR neuroblastoma cells. Dev Brain Res 65:133–146.  https://doi.org/10.1016/0165-3806(92)90172-S CrossRefGoogle Scholar
  56. 56.
    Chen D, Minger SL, Honer WG, Whiteheart S (1999) Organization of the secretory machinery in the rodent brain: distribution of the t-SNAREs, SNAP-25 and SNAP-23. Brain Res 831:11–24.  https://doi.org/10.1016/S0006-8993(99)01371-2 CrossRefPubMedGoogle Scholar
  57. 57.
    Mandolesi G, Vanni V, Cesa R, Grasselli G, Puglisi F, Cesare P, Strata P (2009) Distribution of the SNAP25 and SNAP23 synaptosomal-associated protein isoforms in rat cerebellar cortex. Neuroscience 164:1084–1096.  https://doi.org/10.1016/J.NEUROSCIENCE.2009.08.067 CrossRefPubMedGoogle Scholar
  58. 58.
    Oyler GA (1989) The identification of a novel synaptosomal-associated protein, SNAP-25, differentially expressed by neuronal subpopulations. J Cell Biol 109:3039–3052.  https://doi.org/10.1083/jcb.109.6.3039 CrossRefPubMedGoogle Scholar
  59. 59.
    Holderith N, Lorincz A, Katona G, Rózsa B, Kulik A, Watanabe M, Nusser Z (2012) Release probability of hippocampal glutamatergic terminals scales with the size of the active zone. Nat Neurosci 15:988–997.  https://doi.org/10.1038/nn.3137 CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Kerti K, Lorincz A, Nusser Z (2012) Unique somato-dendritic distribution pattern of Kv4.2 channels on hippocampal CA1 pyramidal cells. Eur J Neurosci 35:66–75.  https://doi.org/10.1111/j.1460-9568.2011.07907.x CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Duc C, Catsicas S (1995) Ultrastructural localization of SNAP-25 within the rat spinal cord and peripheral nervous system. J Comp Neurol 356:152–163.  https://doi.org/10.1002/cne.903560111 CrossRefPubMedGoogle Scholar
  62. 62.
    Ovespian SV, Bodeker M, O’Leary VB, Lawrence GW, Oliver Dolly J (2015) Internalization and retrograde axonal trafficking of tetanus toxin in motor neurons and trans-synaptic propagation at central synapses exceed those of its C-terminal-binding fragments. Brain Struct Funct 220:1825–1838.  https://doi.org/10.1007/s00429-015-1004-0 CrossRefPubMedGoogle Scholar
  63. 63.
    Jones RA, Harrison C, Eaton SL, Llavero Hurtado M, Graham LC, Alkhammash L, Oladiran OA, Gale A et al (2017) Cellular and molecular anatomy of the human neuromuscular junction. Cell Rep 21:2348–2356.  https://doi.org/10.1016/j.celrep.2017.11.008 CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Selak S, Paternain AV, Aller IM, Picó E, Rivera R, Lerma J (2009) A role for SNAP25 in internalization of kainate receptors and synaptic plasticity. Neuron 63:357–371.  https://doi.org/10.1016/j.neuron.2009.07.017 CrossRefPubMedGoogle Scholar
  65. 65.
    Tomasoni R, Repetto D, Morini R, Elia C, Gardoni F, di Luca M, Turco E, Defilippi P et al (2013) SNAP-25 regulates spine formation through postsynaptic binding to p140Cap. Nat Commun 4:2136.  https://doi.org/10.1038/ncomms3136 CrossRefPubMedGoogle Scholar
  66. 66.
    Fossati G, Morini R, Corradini I, Antonucci F, Trepte P, Edry E, Sharma V, Papale A et al (2015) Reduced SNAP-25 increases PSD-95 mobility and impairs spine morphogenesis. Cell Death Differ 22:1425–1436.  https://doi.org/10.1038/cdd.2014.227 CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Tao-Cheng JH, Du J, McBain CJ (2000) SNAP-25 is polarized to axons and abundant along the axolemma: an immunogold study of intact neurons. J Neurocytol 29:67–77.  https://doi.org/10.1023/A:1007168231323 CrossRefPubMedGoogle Scholar
  68. 68.
    Sharma M, Burré J, Bronk P, Zhang Y, Xu W, Südhof TC (2012) CSPα knockout causes neurodegeneration by impairing SNAP-25 function. EMBO J 31:829–841.  https://doi.org/10.1038/emboj.2011.467 CrossRefPubMedGoogle Scholar
  69. 69.
    Pertsinidis A, Mukherjee K, Sharma M, Pang ZP, Park SR, Zhang Y, Brunger AT, Sudhof TC et al (2013) Ultrahigh-resolution imaging reveals formation of neuronal SNARE/Munc18 complexes in situ. Proc Natl Acad Sci U S A 110:E2812–E2820.  https://doi.org/10.1073/pnas.1310654110 CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Genoud S, Pralong W, Riederer BM, Eder L, Catsicas S, Muller D (1999) Activity-dependent phosphorylation of SNAP-25 in hippocampal organotypic cultures. J Neurochem 72:1699–1706.  https://doi.org/10.1046/j.1471-4159.1999.721699.x CrossRefPubMedGoogle Scholar
  71. 71.
    Tanaka C, Nishizuka Y (1994) The protein kinase C family for neuronal signaling. Annu Rev Neurosci 17:551–567.  https://doi.org/10.1146/annurev.ne.17.030194.003003 CrossRefPubMedGoogle Scholar
  72. 72.
    Steinberg SF (2008) Structural basis of protein kinase C isoform function. Physiol Rev 88:1341–1378.  https://doi.org/10.1152/physrev.00034.2007 CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Wang QJ (2006) PKD at the crossroads of DAG and PKC signaling. Trends Pharmacol Sci 27:317–323.  https://doi.org/10.1016/j.tips.2006.04.003 CrossRefPubMedGoogle Scholar
  74. 74.
    Osto E, Kouroedov A, Mocharla P, Akhmedov A, Besler C, Rohrer L, von Eckardstein A, Iliceto S et al (2008) Inhibition of protein kinase Cβ prevents foam cell formation by reducing scavenger receptor A expression in human macrophages. Circulation 118:2174–2182.  https://doi.org/10.1161/CIRCULATIONAHA.108.789537 CrossRefPubMedGoogle Scholar
  75. 75.
    Südhof TC (2012) Calcium control of neurotransmitter release. Cold Spring Harb Perspect Biol 4:a011353.  https://doi.org/10.1101/cshperspect.a011353 CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    de Jong APH, Meijer M, Saarloos I, Cornelisse LN, Toonen RFG, Sørensen JB, Verhage M (2016) Phosphorylation of synaptotagmin-1 controls a post-priming step in PKC-dependent presynaptic plasticity. Proc Natl Acad Sci 113:5095–5100.  https://doi.org/10.1073/pnas.1522927113 CrossRefPubMedGoogle Scholar
  77. 77.
    Wood SJ, Slater CR (2001) Safety factor at the neuromuscular junction. Prog Neurobiol 64:393–429CrossRefGoogle Scholar
  78. 78.
    Sheehan P, Zhu M, Beskow A, Vollmer C, Waites CL (2016) Activity-dependent degradation of synaptic vesicle proteins requires Rab35 and the ESCRT pathway. J Neurosci 36:8668–8686.  https://doi.org/10.1523/JNEUROSCI.0725-16.2016 CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Santafé MM, Salon I, Garcia N, Lanuza MA, Uchitel OD, Tomàs J (2003) Modulation of ACh release by presynaptic muscarinic autoreceptors in the neuromuscular junction of the newborn and adult rat. Eur J Neurosci 17:119–127CrossRefGoogle Scholar
  80. 80.
    Adler M, Sheridan RE, Deshpande SS, Oyler GA (2001) Neuromuscular transmission and muscle contractility in SNAP-25-deficient coloboma mice. Neurotoxicology 22:775–786.  https://doi.org/10.1016/S0161-813X(01)00066-3 CrossRefPubMedGoogle Scholar
  81. 81.
    Huang C-C, Yang D-M, Lin C-C, Kao L-S (2011) Involvement of Rab3A in vesicle priming during exocytosis: interaction with Munc13-1 and Munc18-1. Traffic 12:1356–1370.  https://doi.org/10.1111/j.1600-0854.2011.01237.x CrossRefPubMedGoogle Scholar
  82. 82.
    Rhee JS, Betz A, Pyott S, Reim K, Varoqueaux F, Augustin I, Hesse D, Südhof TC et al (2002) Beta phorbol ester- and diacylglycerol-induced augmentation of transmitter release is mediated by Munc13s and not by PKCs. Cell 108:121–133.  https://doi.org/10.1016/S0092-8674(01)00635-3 CrossRefPubMedGoogle Scholar
  83. 83.
    Derventzi A, Rattan SI, Clark BF (1993) Phorbol ester PMA stimulates protein synthesis and increases the levels of active elongation factors EF-1 alpha and EF-2 in ageing human fibroblasts. Mech Ageing Dev 69:193–205.  https://doi.org/10.1016/0047-6374(93)90023-K CrossRefPubMedGoogle Scholar
  84. 84.
    Takagi Y (2004) Phorbol 12-myristate 13-acetate protects Jurkat cells from methylglyoxal-induced apoptosis by preventing c-Jun N-terminal kinase-mediated leakage of cytochrome c in an extracellular signal-regulated kinase-dependent manner. Mol Pharmacol 65:778–787.  https://doi.org/10.1124/mol.65.3.778 CrossRefPubMedGoogle Scholar
  85. 85.
    Ballif BA, Blenis J (2001) Molecular mechanisms mediating mammalian mitogen-activated protein kinase (MAPK) kinase (MEK)-MAPK cell survival signals. Cell Growth Differ 12:397–408PubMedGoogle Scholar
  86. 86.
    Islamov RR, Samigullin DV, Rizvanov AA, Bondarenko NI, Nikolskiy EE (2015) Synaptosome-associated protein 25 (SNAP25) synthesis in terminal buttons of mouse motor neuron. Dokl Biochem Biophys 464:272–274.  https://doi.org/10.1134/S1607672915050026 CrossRefPubMedGoogle Scholar
  87. 87.
    Alkon DL, Epstein H, Kuzirian A, Bennett MC, Nelson TJ (2005) Protein synthesis required for long-term memory is induced by PKC activation on days before associative learning. Proc Natl Acad Sci U S A 102:16432–16437.  https://doi.org/10.1073/pnas.0508001102 CrossRefPubMedPubMedCentralGoogle Scholar
  88. 88.
    Hongpaisan J, Xu C, Sen A, Nelson TJ, Alkon DL (2013) PKC activation during training restores mushroom spine synapses and memory in the aged rat. Neurobiol Dis 55:44–62.  https://doi.org/10.1016/j.nbd.2013.03.012 CrossRefPubMedGoogle Scholar
  89. 89.
    Larburu N, Montellese C, O’Donohue M-F et al (2016) Structure of a human pre-40S particle points to a role for RACK1 in the final steps of 18S rRNA processing. Nucleic Acids Res 44:8465–8478.  https://doi.org/10.1093/nar/gkw714 CrossRefPubMedPubMedCentralGoogle Scholar
  90. 90.
    Lee H-W, Smith L, Pettit GR, Vinitsky A, Smith JB (1996) Ubiquitination of protein kinase C-alpha and degradation by the proteasome. J Biol Chem 271:20973–20976.  https://doi.org/10.1074/jbc.271.35.20973 CrossRefPubMedGoogle Scholar
  91. 91.
    Kang BS, French OG, Sando JJ, Hahn CS (2000) Activation-dependent degradation of protein kinase C eta. Oncogene 19:4263–4272.  https://doi.org/10.1038/sj.onc.1203779 CrossRefPubMedGoogle Scholar
  92. 92.
    Garcia N, Priego M, Obis T, Santafe MM, Tomàs M, Besalduch N, Lanuza MA, Tomàs J (2013) Adenosine A1 and A2A receptor-mediated modulation of acetylcholine release in the mice neuromuscular junction. Eur J Neurosci 38:2229–2241CrossRefGoogle Scholar
  93. 93.
    Santafé MM, Priego M, Obis T et al (2015) Adenosine receptors and muscarinic receptors cooperate in acetylcholine release modulation in the neuromuscular synapse. Eur J Neurosci 42:1775–1787.  https://doi.org/10.1111/ejn.12922 CrossRefPubMedGoogle Scholar
  94. 94.
    Tomàs J, Garcia N, Lanuza MA, Santafé MM, Tomàs M, Nadal L, Hurtado E, Simó-Ollé A et al (2018) Adenosine receptors in developing and adult mouse neuromuscular junctions and functional links with other metabotropic receptor. Pathways 9:1–10.  https://doi.org/10.3389/fphar.2018.00397 CrossRefGoogle Scholar
  95. 95.
    Ross EM, Berstein G (1993) Regulation of the M1 muscarinic receptor-Gq-phospholipase C-beta pathway by nucleotide exchange and GTP hydrolysis. Life Sci 52:413–419.  https://doi.org/10.1016/0024-3205(93)90296-F CrossRefPubMedGoogle Scholar
  96. 96.
    Biddlecome GH, Berstein G, Ross EM (1996) Regulation of phospholipase C-beta1 by Gq and m1 muscarinic cholinergic receptor. Steady-state balance of receptor-mediated activation and GTPase-activating protein-promoted deactivation. J Biol Chem 271:7999–8007.  https://doi.org/10.1074/JBC.271.14.7999 CrossRefPubMedGoogle Scholar
  97. 97.
    Strassheim D, Williams CL (2000) P2Y2 purinergic and M3 muscarinic acetylcholine receptors activate different phospholipase C-beta isoforms that are uniquely susceptible to protein kinase C-dependent phosphorylation and inactivation. J Biol Chem 275:39767–39772.  https://doi.org/10.1074/jbc.M007775200 CrossRefPubMedGoogle Scholar
  98. 98.
    Middlemas DS, Meisenhelder J, Hunter T (1994) Identification of TrkB autophosphorylation sites and evidence that phospholipase C-gamma 1 is a substrate of the TrkB receptor. J Biol Chem 269:5458–5466PubMedGoogle Scholar
  99. 99.
    Proenca CC, Song M, Lee FS (2016) Differential effects of BDNF and neurotrophin 4 (NT4) on endocytic sorting of TrkB receptors. J Neurochem 138:397–406.  https://doi.org/10.1111/jnc.13676 CrossRefPubMedPubMedCentralGoogle Scholar
  100. 100.
    Garcia N, Tomàs M, Santafé MM et al (2010) Localization of brain-derived neurotrophic factor, neurotrophin-4, tropomyosin-related kinase b receptor, and p75 NTR receptor by high-resolution immunohistochemistry on the adult mouse neuromuscular junction. J Peripher Nerv Syst 15:40–49.  https://doi.org/10.1111/j.1529-8027.2010.00250.x CrossRefPubMedGoogle Scholar
  101. 101.
    Mantilla CB, Stowe JM, Sieck DC, Ermilov LG, Greising SM, Zhang C, Shokat KM, Sieck GC (2014) TrkB kinase activity maintains synaptic function and structural integrity at adult neuromuscular junctions. J Appl Physiol 117:910–920.  https://doi.org/10.1152/japplphysiol.01386.2013 CrossRefPubMedPubMedCentralGoogle Scholar
  102. 102.
    Sharma M, Burré J, Südhof TC (2011) CSPα promotes SNARE-complex assembly by chaperoning SNAP-25 during synaptic activity. Nat Cell Biol 13:30–39.  https://doi.org/10.1038/ncb2131 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Unitat d’Histologia i Neurobiologia (UHNEUROB), Facultat de Medicina i Ciències de la SalutUniversitat Rovira i VirgiliReusSpain

Personalised recommendations