Frontiers in Biology

, Volume 7, Issue 5, pp 379–396 | Cite as

Structure and function of the guanylate kinase-like domain of the MAGUK family scaffold proteins

  • Jinwei Zhu
  • Yuan Shang
  • Jia Chen
  • Mingjie ZhangEmail author


Membrane associated guanylate kinases (MAGUKs) are a family of scaffold proteins that play essential roles in organ development, cell-cell communication, cell polarity establishment and maintenance, and cellular signal transduction. Every member of the MAGUK family contains a guanylate kinase-like (GK) domain, which has evolved from the enzyme catalyzing GMP to GDP conversion to become a protein-protein interaction module with no enzymatic activity.Mutations of MAGUKs are linked to a number of human diseases, including autism and hereditary deafness. In this review, we summarize the structural basis governing cellular function of various members of the MAGUKs. In particular, we focus on recent discoveries of MAGUK GKs as specific phospho-protein interaction modules, and discuss functional implications and connections to human diseases of such regulated MAGUK GK/target interactions.


MAGUK GK domain phospho-protein interaction module synapse neuronal disease 


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  1. Anderson J M (1996). Cell signalling: MAGUK magic. Curr Biol, 6(4): 382–384PubMedCrossRefGoogle Scholar
  2. Aoki C, Miko I, Oviedo H, Mikeladze-Dvali T, Alexandre L, Sweeney N, Bredt D S (2001). Electron microscopic immunocytochemical detection of PSD-95, PSD-93, SAP-102, and SAP-97 at postsynaptic, presynaptic, and nonsynaptic sites of adult and neonatal rat visual cortex. Synapse, 40(4): 239–257PubMedCrossRefGoogle Scholar
  3. Asaba N, Hanada T, Takeuchi A, Chishti A H (2003). Direct interaction with a kinesin-related motor mediates transport of mammalian discs large tumor suppressor homologue in epithelial cells. J Biol Chem, 278(10): 8395–8400PubMedCrossRefGoogle Scholar
  4. Bangash M A, Park J M, Melnikova T, Wang D, Jeon S K, Lee D, Syeda S, Kim J, Kouser M, Schwartz J, Cui Y, Zhao X, Speed H E, Kee S E, Tu J C, Hu J H, Petralia R S, Linden D J, Powell C M, Savonenko A, Xiao B, Worley P F (2011). Enhanced polyubiquitination of Shank3 and NMDA receptor in a mouse model of autism. Cell, 145(5): 758–772PubMedCrossRefGoogle Scholar
  5. Bellaïche Y, Radovic A, Woods D F, Hough C D, Parmentier M L, O’Kane C J, Bryant P J, Schweisguth F (2001). The Partner of Inscuteable/Discs-large complex is required to establish planar polarity during asymmetric cell division in Drosophila. Cell, 106(3): 355–366PubMedCrossRefGoogle Scholar
  6. Bienvenu O J, Wang Y, Shugart Y Y, Welch JM, Grados MA, Fyer A J, Rauch S L, McCracken J T, Rasmussen S A, Murphy D L, Cullen B, Valle D, Hoehn-Saric R, Greenberg B D, Pinto A, Knowles J A, Piacentini J, Pauls D L, Liang K Y, Willour V L, Riddle M, Samuels J F, Feng G, Nestadt G (2009). Sapap3 and pathological grooming in humans: Results from the OCD collaborative genetics study. Am J Med Genet B Neuropsychiatr Genet, 150B(5): 710–720PubMedCrossRefGoogle Scholar
  7. Blonska M, Lin X (2011). NF-κB signaling pathways regulated by CARMA family of scaffold proteins. Cell Res, 21(1): 55–70PubMedCrossRefGoogle Scholar
  8. Böckers T M, Mameza M G, Kreutz M R, Bockmann J, Weise C, Buck F, Richter D, Gundelfinger E D, Kreienkamp H J (2001). Synaptic scaffolding proteins in rat brain. Ankyrin repeats of the multidomain Shank protein family interact with the cytoskeletal protein alphafodrin. J Biol Chem, 276(43): 40104–40112PubMedCrossRefGoogle Scholar
  9. Borg J P, Straight S W, Kaech S M, de Taddéo-Borg M, Kroon D E, Karnak D, Turner R S, Kim S K, Margolis B (1998). Identification of an evolutionarily conserved heterotrimeric protein complex involved in protein targeting. J Biol Chem, 273(48): 31633–31636PubMedCrossRefGoogle Scholar
  10. Brenman J E, Topinka J R, Cooper E C, McGee AW, Rosen J, Milroy T, Ralston H J, Bredt D S (1998). Localization of postsynaptic density-93 to dendritic microtubules and interaction with microtubuleassociated protein 1A. J Neurosci, 18(21): 8805–8813PubMedGoogle Scholar
  11. Butz S, Okamoto M, Südhof T C (1998). A tripartite protein complex with the potential to couple synaptic vesicle exocytosis to cell adhesion in brain. Cell, 94(6): 773–782PubMedCrossRefGoogle Scholar
  12. Chen Y, Sheng R, Källberg M, Silkov A, Tun M P, Bhardwaj N, Kurilova S, Hall R A, Honig B, Lu H, Cho W (2012). Genome-wide functional annotation of dual-specificity protein- and lipid-binding modules that regulate protein interactions. Mol Cell, 46(2): 226–237PubMedCrossRefGoogle Scholar
  13. Chen Y H, Li M H, Zhang Y, He L L, Yamada Y, Fitzmaurice A, Shen Y, Zhang H, Tong L, Yang J (2004). Structural basis of the alpha1-beta subunit interaction of voltage-gated Ca2+ channels. Nature, 429(6992): 675–680PubMedCrossRefGoogle Scholar
  14. Cheng D, Hoogenraad C C, Rush J, Ramm E, Schlager M A, Duong D M, Xu P, Wijayawardana S R, Hanfelt J, Nakagawa T, Sheng M, Peng J (2006). Relative and absolute quantification of postsynaptic density proteome isolated from rat forebrain and cerebellum. Mol Cell Proteomics, 5(6): 1158–1170PubMedCrossRefGoogle Scholar
  15. Cohen A R, Woods D F, Marfatia S M, Walther Z, Chishti A H, Anderson J M (1998). Human CASK/LIN-2 binds syndecan-2 and protein 4.1 and localizes to the basolateral membrane of epithelial cells. J Cell Biol, 142(1): 129–138PubMedCrossRefGoogle Scholar
  16. Colledge M, Dean R A, Scott G K, Langeberg L K, Huganir R L, Scott J D (2000). Targeting of PKA to glutamate receptors through a MAGUK-AKAP complex. Neuron, 27(1): 107–119PubMedCrossRefGoogle Scholar
  17. de Mendoza A, Suga H, Ruiz-Trillo I (2010). Evolution of the MAGUK protein gene family in premetazoan lineages. BMC Evol Biol, 10(1): 93PubMedCrossRefGoogle Scholar
  18. Deguchi M, Hata Y, Takeuchi M, Ide N, Hirao K, Yao I, Irie M, Toyoda A, Takai Y (1998). BEGAIN (brain-enriched guanylate kinaseassociated protein), a novel neuronal PSD-95/SAP90-binding protein. J Biol Chem, 273(41): 26269–26272PubMedCrossRefGoogle Scholar
  19. Doe C Q (2008). Neural stem cells: balancing self-renewal with differentiation. Development, 135(9): 1575–1587PubMedCrossRefGoogle Scholar
  20. Doerks T, Bork P, Kamberov E, Makarova O, Muecke S, Margolis B (2000). L27, a novel heterodimerization domain in receptor targeting proteins Lin-2 and Lin-7. Trends Biochem Sci, 25(7): 317–318PubMedCrossRefGoogle Scholar
  21. Durand C M, Betancur C, Boeckers T M, Bockmann J, Chaste P, Fauchereau F, Nygren G, Rastam M, Gillberg I C, Anckarsäter H, Sponheim E, Goubran-Botros H, Delorme R, Chabane N, Mouren-Simeoni M C, de Mas P, Bieth E, Rogé B, Héron D, Burglen L, Gillberg C, Leboyer M, Bourgeron T (2007). Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders. Nat Genet, 39(1): 25–27PubMedCrossRefGoogle Scholar
  22. Fanning A S, Jameson B J, Jesaitis L A, Anderson J M (1998). The tight junction protein ZO-1 establishes a link between the transmembrane protein occludin and the actin cytoskeleton. J Biol Chem, 273(45): 29745–29753PubMedCrossRefGoogle Scholar
  23. Fanning A S, Little B P, Rahner C, Utepbergenov D, Walther Z, Anderson J M (2007). The unique-5 and -6 motifs of ZO-1 regulate tight junction strand localization and scaffolding properties. Mol Biol Cell, 18(3): 721–731PubMedCrossRefGoogle Scholar
  24. Feng W, Long J F, Fan J S, Suetake T, Zhang M (2004). The tetrameric L27 domain complex as an organization platform for supramolecular assemblies. Nat Struct Mol Biol, 11(5): 475–480PubMedCrossRefGoogle Scholar
  25. Feng W, Long J F, Zhang M (2005). A unified assembly mode revealed by the structures of tetrameric L27 domain complexes formed by mLin-2/mLin-7 and Patj/Pals1 scaffold proteins. Proc Natl Acad Sci USA, 102(19): 6861–6866PubMedCrossRefGoogle Scholar
  26. Feng W, Zhang M (2009). Organization and dynamics of PDZ-domainrelated supramodules in the postsynaptic density. Nat Rev Neurosci, 10(2): 87–99PubMedCrossRefGoogle Scholar
  27. Feyder M, Karlsson R M, Mathur P, Lyman M, Bock R, Momenan R, Munasinghe J, Scattoni M L, Ihne J, Camp M, Graybeal C, Strathdee D, Begg A, Alvarez V A, Kirsch P, Rietschel M, Cichon S, Walter H, Meyer-Lindenberg A, Grant S G, Holmes A (2010). Association of mouse Dlg4 (PSD-95) gene deletion and human DLG4 gene variation with phenotypes relevant to autism spectrum disorders and Williams’ syndrome. Am J Psychiatry, 167(12): 1508–1517PubMedCrossRefGoogle Scholar
  28. Froyen G, Van Esch H, Bauters M, Hollanders K, Frints S G, Vermeesch J R, Devriendt K, Fryns J P, Marynen P (2007). Detection of genomic copy number changes in patients with idiopathic mental retardation by high-resolution X-array-CGH: important role for increased gene dosage of XLMR genes. Hum Mutat, 28(10): 1034–1042PubMedCrossRefGoogle Scholar
  29. Funke L, Dakoji S, Bredt D S (2005). Membrane-associated guanylate kinases regulate adhesion and plasticity at cell junctions. Annu Rev Biochem, 74(1): 219–245PubMedCrossRefGoogle Scholar
  30. Garcia E P, Mehta S, Blair L A, Wells D G, Shang J, Fukushima T, Fallon J R, Garner C C, Marshall J (1998). SAP90 binds and clusters kainate receptors causing incomplete desensitization. Neuron, 21(4): 727–739PubMedCrossRefGoogle Scholar
  31. Geschwind D H (2009). Advances in autism. Annu Rev Med, 60(1): 367–380PubMedCrossRefGoogle Scholar
  32. Gillies T E, Cabernard C (2011). Cell division orientation in animals. Curr Biol, 21(15): R599–R609PubMedCrossRefGoogle Scholar
  33. González-Mariscal L, Betanzos A, Avila-Flores A (2000). MAGUK proteins: structure and role in the tight junction. Semin Cell Dev Biol, 11(4): 315–324PubMedCrossRefGoogle Scholar
  34. Gosens I, van Wijk E, Kersten F F, Krieger E, van der Zwaag B, Märker T, Letteboer S J, Dusseljee S, Peters T, Spierenburg H A, Punte I M, Wolfrum U, Cremers F P, Kremer H, Roepman R (2007). MPP1 links the Usher protein network and the Crumbs protein complex in the retina. Hum Mol Genet, 16(16): 1993–2003PubMedCrossRefGoogle Scholar
  35. Hackett A, Tarpey P S, Licata A, Cox J, Whibley A, Boyle J, Rogers C, Grigg J, Partington M, Stevenson R E, Tolmie J, Yates J R, Turner G, Wilson M, Futreal A P, Corbett M, Shaw M, Gecz J, Raymond F L, Stratton M R, Schwartz C E, Abidi F E (2010). CASK mutations are frequent in males and cause X-linked nystagmus and variable XLMR phenotypes. Eur J Hum Genet, 18(5): 544–552PubMedCrossRefGoogle Scholar
  36. Hall S W, Kühn H (1986). Purification and properties of guanylate kinase from bovine retinas and rod outer segments. Eur J Biochem, 161(3): 551–556PubMedCrossRefGoogle Scholar
  37. Hanada T, Lin L, Tibaldi E V, Reinherz E L, Chishti A H (2000). GAKIN, a novel kinesin-like protein associates with the human homologue of the Drosophila discs large tumor suppressor in T lymphocytes. J Biol Chem, 275(37): 28774–28784PubMedCrossRefGoogle Scholar
  38. Hao Y, Du Q, Chen X, Zheng Z, Balsbaugh J L, Maitra S, Shabanowitz J, Hunt D F, Macara I G (2010). Par3 controls epithelial spindle orientation by aPKC-mediated phosphorylation of apical Pins. Curr Biol, 20(20): 1809–1818PubMedCrossRefGoogle Scholar
  39. Hata Y, Butz S, Südhof T C (1996). CASK: a novel dlg/PSD95 homolog with an N-terminal calmodulin-dependent protein kinase domain identified by interaction with neurexins. J Neurosci, 16(8): 2488–2494PubMedGoogle Scholar
  40. Hayashi S, Mizuno S, Migita O, Okuyama T, Makita Y, Hata A, Imoto I, Inazawa J (2008). The CASK gene harbored in a deletion detected by array-CGH as a potential candidate for a gene causative of X-linked dominant mental retardation. Am J Med Genet A, 146A(16): 2145–2151PubMedCrossRefGoogle Scholar
  41. Hirao K, Hata Y, Ide N, Takeuchi M, Irie M, Yao I, Deguchi M, Toyoda A, Sudhof T C, Takai Y (1998). A novel multiple PDZ domaincontaining molecule interacting with N-methyl-D-aspartate receptors and neuronal cell adhesion proteins. J Biol Chem, 273(33): 21105–21110PubMedCrossRefGoogle Scholar
  42. Hoskins R, Hajnal A F, Harp S A, Kim S K (1996). The C. elegans vulval induction gene lin-2 encodes a member of the MAGUK family of cell junction proteins. Development, 122(1): 97–111PubMedGoogle Scholar
  43. Hsueh Y P (2009). Calcium/calmodulin-dependent serine protein kinase and mental retardation. Ann Neurol, 66(4): 438–443PubMedCrossRefGoogle Scholar
  44. Hsueh Y P, Wang T F, Yang F C, Sheng M (2000). Nuclear translocation and transcription regulation by the membrane-associated guanylate kinase CASK/LIN-2. Nature, 404(6775): 298–302PubMedCrossRefGoogle Scholar
  45. Huang T N, Chang H P, Hsueh Y P (2010). CASK phosphorylation by PKA regulates the protein-protein interactions of CASK and expression of the NMDAR2b gene. J Neurochem, 112(6): 1562–1573PubMedCrossRefGoogle Scholar
  46. Huang T N, Hsueh Y P (2009). CASK point mutation regulates proteinprotein interactions and NR2b promoter activity. Biochem Biophys Res Commun, 382(1): 219–222PubMedCrossRefGoogle Scholar
  47. Hung A Y, Sheng M (2002). PDZ domains: structural modules for protein complex assembly. J Biol Chem, 277(8): 5699–5702PubMedCrossRefGoogle Scholar
  48. Hutterer A, Berdnik D, Wirtz-Peitz F, Zigman M, Schleiffer A, Knoblich J A (2006). Mitotic activation of the kinase Aurora-A requires its binding partner Bora. Dev Cell, 11(2): 147–157PubMedCrossRefGoogle Scholar
  49. Johnston C A, Doe C Q, Prehoda K E (2012). Structure of an enzymederived phosphoprotein recognition domain. PLoS ONE, 7(4): e36014PubMedCrossRefGoogle Scholar
  50. Johnston C A, Hirono K, Prehoda K E, Doe C Q (2009). Identification of an Aurora-A/PinsLINKER/Dlg spindle orientation pathway using induced cell polarity in S2 cells. Cell, 138(6): 1150–1163PubMedCrossRefGoogle Scholar
  51. Johnston C A, Whitney D S, Volkman B F, Doe C Q, Prehoda K E (2011). Conversion of the enzyme guanylate kinase into a mitoticspindle orienting protein by a single mutation that inhibits GMPinduced closing. Proc Natl Acad Sci USA, 108(44): E973–E978PubMedCrossRefGoogle Scholar
  52. Kim E, Naisbitt S, Hsueh Y P, Rao A, Rothschild A, Craig A M, Sheng M (1997). GKAP, a novel synaptic protein that interacts with the guanylate kinase-like domain of the PSD-95/SAP90 family of channel clustering molecules. J Cell Biol, 136(3): 669–678PubMedCrossRefGoogle Scholar
  53. Kistner U, Garner C C, Linial M (1995). Nucleotide binding by the synapse associated protein SAP90. FEBS Lett, 359(2–3): 159–163PubMedCrossRefGoogle Scholar
  54. Knoblich J A (2008). Mechanisms of asymmetric stem cell division. Cell, 132(4): 583–597PubMedCrossRefGoogle Scholar
  55. Kuhlendahl S, Spangenberg O, Konrad M, Kim E, Garner C C (1998). Functional analysis of the guanylate kinase-like domain in the synapse-associated protein SAP97. Eur J Biochem, 252(2): 305–313PubMedCrossRefGoogle Scholar
  56. Li Y, Zhang Y L, Yan H G (1996). Kinetic and thermodynamic characterizations of yeast guanylate kinase. J Biol Chem, 271(45): 28038–28044PubMedCrossRefGoogle Scholar
  57. Lu B, Jan L, Jan Y N (2000). Control of cell divisions in the nervous system: symmetry and asymmetry. Annu Rev Neurosci, 23(1): 531–556PubMedCrossRefGoogle Scholar
  58. Lu X J, Chen X Q, Weng J, Zhang H Y, Pak D T, Luo J H, Du J Z (2009). Hippocampal spine-associated Rap-specific GTPase-activating protein induces enhancement of learning and memory in postnatally hypoxia-exposed mice. Neuroscience, 162(2): 404–414PubMedCrossRefGoogle Scholar
  59. Lye M F, Fanning A S, Su Y, Anderson J M, Lavie A (2010). Insights into regulated ligand binding sites from the structure of ZO-1 Src homology 3-guanylate kinase module. J Biol Chem, 285(18): 13907–13917PubMedCrossRefGoogle Scholar
  60. Masuko N, Makino K, Kuwahara H, Fukunaga K, Sudo T, Araki N, Yamamoto H, Yamada Y, Miyamoto E, Saya H (1999). Interaction of NE-dlg/SAP102, a neuronal and endocrine tissue-specific membrane-associated guanylate kinase protein, with calmodulin and PSD-95/SAP90. A possible regulatory role in molecular clustering at synaptic sites. J Biol Chem, 274(9): 5782–5790Google Scholar
  61. Maximov A, Südhof T C, Bezprozvanny I (1999). Association of neuronal calcium channels with modular adaptor proteins. J Biol Chem, 274(35): 24453–24456PubMedCrossRefGoogle Scholar
  62. Mburu P, Kikkawa Y, Townsend S, Romero R, Yonekawa H, Brown S D (2006). Whirlin complexes with p55 at the stereocilia tip during hair cell development. Proc Natl Acad Sci USA, 103(29): 10973–10978PubMedCrossRefGoogle Scholar
  63. McGee A W, Bredt D S (1999). Identification of an intramolecular interaction between the SH3 and guanylate kinase domains of PSD-95. J Biol Chem, 274(25): 17431–17436PubMedCrossRefGoogle Scholar
  64. McGee A W, Dakoji S R, Olsen O, Bredt D S, Lim W A, Prehoda K E (2001). Structure of the SH3-guanylate kinase module from PSD-95 suggests a mechanism for regulated assembly of MAGUK scaffolding proteins. Mol Cell, 8(6): 1291–1301PubMedCrossRefGoogle Scholar
  65. McGee AW, Nunziato D A, Maltez J M, Prehoda K E, Pitt G S, Bredt D S (2004). Calcium channel function regulated by the SH3-GK module in beta subunits. Neuron, 42(1): 89–99PubMedCrossRefGoogle Scholar
  66. Moessner R, Marshall C R, Sutcliffe J S, Skaug J, Pinto D, Vincent J, Zwaigenbaum L, Fernandez B, Roberts W, Szatmari P, Scherer S W (2007). Contribution of SHANK3 mutations to autism spectrum disorder. Am J Hum Genet, 81(6): 1289–1297PubMedCrossRefGoogle Scholar
  67. Montgomery J M, Zamorano P L, Garner C C (2004). MAGUKs in synapse assembly and function: an emerging view. Cell Mol Life Sci, 61(7–8): 911–929PubMedCrossRefGoogle Scholar
  68. Moog U, Kutsche K, Kortüm F, Chilian B, Bierhals T, Apeshiotis N, Balg S, Chassaing N, Coubes C, Das S, Engels H, Van Esch H, Grasshoff U, Heise M, Isidor B, Jarvis J, Koehler U, Martin T, Oehl-Jaschkowitz B, Ortibus E, Pilz D T, Prabhakar P, Rappold G, Rau I, Rettenberger G, Schlüter G, Scott R H, Shoukier M, Wohlleber E, Zirn B, Dobyns W B, Uyanik G (2011). Phenotypic spectrum associated with CASK loss-of-function mutations. J Med Genet, 48(11): 741–751PubMedCrossRefGoogle Scholar
  69. Mortier E, Wuytens G, Leenaerts I, Hannes F, Heung M Y, Degeest G, David G, Zimmermann P (2005). Nuclear speckles and nucleoli targeting by PIP2-PDZ domain interactions. EMBO J, 24(14): 2556–2565PubMedCrossRefGoogle Scholar
  70. Naisbitt S, Kim E, Tu J C, Xiao B, Sala C, Valtschanoff J, Weinberg R J, Worley P F, Sheng M (1999). Shank, a novel family of postsynaptic density proteins that binds to the NMDA receptor/PSD-95/GKAP complex and cortactin. Neuron, 23(3): 569–582PubMedCrossRefGoogle Scholar
  71. Naisbitt S, Valtschanoff J, Allison D W, Sala C, Kim E, Craig A M, Weinberg R J, Sheng M (2000). Interaction of the postsynaptic density-95/guanylate kinase domain-associated protein complex with a light chain of myosin-V and dynein. J Neurosci, 20(12): 4524–4534PubMedGoogle Scholar
  72. Najm J, Horn D, Wimplinger I, Golden J A, Chizhikov V V, Sudi J, Christian S L, Ullmann R, Kuechler A, Haas C A, Flubacher A, Charnas L R, Uyanik G, Frank U, Klopocki E, Dobyns WB, Kutsche K (2008). Mutations of CASK cause an X-linked brain malformation phenotype with microcephaly and hypoplasia of the brainstem and cerebellum. Nat Genet, 40(9): 1065–1067PubMedCrossRefGoogle Scholar
  73. Nomme J, Fanning A S, Caffrey M, Lye M F, Anderson J M, Lavie A (2011). The Src homology 3 domain is required for junctional adhesion molecule binding to the third PDZ domain of the scaffolding protein ZO-1. J Biol Chem, 286(50): 43352–43360PubMedCrossRefGoogle Scholar
  74. Oliva C, Escobedo P, Astorga C, Molina C, Sierralta J (2012). Role of the MAGUK protein family in synapse formation and function. Dev Neurobiol, 72(1): 57–72PubMedCrossRefGoogle Scholar
  75. Olsen O, Bredt D S (2003). Functional analysis of the nucleotide binding domain of membrane-associated guanylate kinases. J Biol Chem, 278(9): 6873–6878PubMedCrossRefGoogle Scholar
  76. Olsen O, Funke L, Long J F, Fukata M, Kazuta T, Trinidad J C, Moore K A, Misawa H, Welling P A, Burlingame A L, Zhang M, Bredt D S (2007). Renal defects associated with improper polarization of the CRB and DLG polarity complexes in MALS-3 knockout mice. J Cell Biol, 179(1): 151–164PubMedCrossRefGoogle Scholar
  77. Olsen O, Moore K A, Fukata M, Kazuta T, Trinidad J C, Kauer F W, Streuli M, Misawa H, Burlingame A L, Nicoll R A, Bredt D S (2005). Neurotransmitter release regulated by a MALS-liprin-alpha presynaptic complex. J Cell Biol, 170(7): 1127–1134PubMedCrossRefGoogle Scholar
  78. Opatowsky Y, Chen C C, Campbell K P, Hirsch J A (2004). Structural analysis of the voltage-dependent calcium channel beta subunit functional core and its complex with the alpha 1 interaction domain. Neuron, 42(3): 387–399PubMedCrossRefGoogle Scholar
  79. Pak D T, Yang S, Rudolph-Correia S, Kim E, Sheng M (2001). Regulation of dendritic spine morphology by SPAR, a PSD-95-associated RapGAP. Neuron, 31(2): 289–303PubMedCrossRefGoogle Scholar
  80. Pan L, Chen J, Yu J, Yu H, Zhang M (2011). The structure of the PDZ3-SH3-GuK tandem of ZO-1 protein suggests a supramodular organization of the membrane-associated guanylate kinase (MAGUK) family scaffold protein core. J Biol Chem, 286(46): 40069–40074PubMedCrossRefGoogle Scholar
  81. Pan L, Zhang M (2012). Structures of usher syndrome 1 proteins and their complexes. Physiology (Bethesda), 27(1): 25–42CrossRefGoogle Scholar
  82. Pawson T (2004). Specificity in signal transduction: from phosphotyrosine-SH2 domain interactions to complex cellular systems. Cell, 116(2): 191–203PubMedCrossRefGoogle Scholar
  83. Peça J, Feliciano C, Ting J T, Wang W, Wells M F, Venkatraman T N, Lascola C D, Fu Z, Feng G (2011). SHANK3 mutant mice display autistic-like behaviours and striatal dysfunction. Nature, 472(7344): 437–442PubMedCrossRefGoogle Scholar
  84. Peca J, Feng G (2012). Cellular and synaptic network defects in autism. Curr Opin Neurobiol, 22: 1–7CrossRefGoogle Scholar
  85. Piluso G, D’Amico F, Saccone V, Bismuto E, Rotundo I L, Di Domenico M, Aurino S, Schwartz C E, Neri G, Nigro V (2009). A missense mutation in CASK causes FG syndrome in an Italian family. Am J Hum Genet, 84(2): 162–177PubMedCrossRefGoogle Scholar
  86. Quinn B J, Welch E J, Kim A C, Lokuta M A, Huttenlocher A, Khan A A, Kuchay S M, Chishti A H (2009). Erythrocyte scaffolding protein p55/MPP1 functions as an essential regulator of neutrophil polarity. Proc Natl Acad Sci U S A, 106(47): 19842–19847PubMedGoogle Scholar
  87. Roh M H, Makarova O, Liu C J, Shin K, Lee S, Laurinec S, Goyal M, Wiggins R, Margolis B (2002). The Maguk protein, Pals1, functions as an adapter, linking mammalian homologues of Crumbs and Discs Lost. J Cell Biol, 157(1): 161–172PubMedCrossRefGoogle Scholar
  88. Samuels B A, Hsueh Y P, Shu T, Liang H, Tseng H C, Hong C J, Su S C, Volker J, Neve R L, Yue D T, Tsai L H (2007). Cdk5 promotes synaptogenesis by regulating the subcellular distribution of the MAGUK family member CASK. Neuron, 56(5): 823–837PubMedCrossRefGoogle Scholar
  89. Schmeisser M J, Ey E, Wegener S, Bockmann J, Stempel A V, Kuebler A, Janssen A-L, Udvardi P T, Shiban E, Spilker C, Balschun D, Skryabin B V, Dieck S T, Smalla K-H, Montag D, Leblond C S, Faure P, Torquet N, Le Sourd A-M, Toro R, Grabrucker AM, Shoichet S A, Schmitz D, Kreutz MR, Bourgeron T, Gundelfinger E D, Boeckers T M (2012). Autistic-like behaviours and hyperactivity in mice lacking ProSAP1/Shank2. Nature, advance online publicationGoogle Scholar
  90. Shin H, Hsueh Y P, Yang F C, Kim E, Sheng M (2000). An intramolecular interaction between Src homology 3 domain and guanylate kinase-like domain required for channel clustering by postsynaptic density-95/SAP90. J Neurosci, 20(10): 3580–3587PubMedGoogle Scholar
  91. Siegrist S E, Doe C Q (2005). Microtubule-induced Pins/Galphai cortical polarity in Drosophila neuroblasts. Cell, 123(7): 1323–1335PubMedCrossRefGoogle Scholar
  92. Siller K H, Doe C Q (2009). Spindle orientation during asymmetric cell division. Nat Cell Biol, 11(4): 365–374PubMedCrossRefGoogle Scholar
  93. Stehle T, Schulz G E (1990). Three-dimensional structure of the complex of guanylate kinase from yeast with its substrate GMP. J Mol Biol, 211(1): 249–254PubMedCrossRefGoogle Scholar
  94. Stehle T, Schulz G E (1992). Refined structure of the complex between guanylate kinase and its substrate GMP at 2.0 A resolution. J Mol Biol, 224(4): 1127–1141PubMedCrossRefGoogle Scholar
  95. Sun M, Liu L, Zeng X, Xu M, Liu L, Fang M, Xie W (2009). Genetic interaction between Neurexin and CAKI/CMG is important for synaptic function in Drosophila neuromuscular junction. Neurosci Res, 64(4): 362–371PubMedCrossRefGoogle Scholar
  96. Tabuchi K, Biederer T, Butz S, Sudhof T C (2002). CASK participates in alternative tripartite complexes in which Mint 1 competes for binding with caskin 1, a novel CASK-binding protein. J Neurosci, 22(11): 4264–4273PubMedGoogle Scholar
  97. Takahashi S X, Miriyala J, Tay L H, Yue D T, Colecraft H M (2005). A CaVbeta SH3/guanylate kinase domain interaction regulates multiple properties of voltage-gated Ca2+ channels. J Gen Physiol, 126(4): 365–377PubMedCrossRefGoogle Scholar
  98. Tanentzapf G, Tepass U (2003). Interactions between the crumbs, lethal giant larvae and bazooka pathways in epithelial polarization. Nat Cell Biol, 5(1): 46–52PubMedCrossRefGoogle Scholar
  99. Tarpey P, Parnau J, Blow M, Woffendin H, Bignell G, Cox C, Cox J, Davies H, Edkins S, Holden S, Korny A, Mallya U, Moon J, O’Meara S, Parker A, Stephens P, Stevens C, Teague J, Donnelly A, Mangelsdorf M, Mulley J, Partington M, Turner G, Stevenson R, Schwartz C, Young I, Easton D, Bobrow M, Futreal P A, Stratton M R, Gecz J, Wooster R, Raymond F L (2004). Mutations in the DLG3 gene cause nonsyndromic X-linked mental retardation. Am J Hum Genet, 75(2): 318–324PubMedCrossRefGoogle Scholar
  100. Tarpey P S, Smith R, Pleasance E, Whibley A, Edkins S, Hardy C, O’Meara S, Latimer C, Dicks E, Menzies A, Stephens P, Blow M, Greenman C, Xue Y, Tyler-Smith C, Thompson D, Gray K, Andrews J, Barthorpe S, Buck G, Cole J, Dunmore R, Jones D, Maddison M, Mironenko T, Turner R, Turrell K, Varian J, West S, Widaa S, Wray P, Teague J, Butler A, Jenkinson A, Jia M, Richardson D, Shepherd R, Wooster R, Tejada M I, Martinez F, Carvill G, Goliath R, de Brouwer A P, van Bokhoven H, Van Esch H, Chelly J, Raynaud M, Ropers H H, Abidi F E, Srivastava A K, Cox J, Luo Y, Mallya U, Moon J, Parnau J, Mohammed S, Tolmie J L, Shoubridge C, Corbett M, Gardner A, Haan E, Rujirabanjerd S, Shaw M, Vandeleur L, Fullston T, Easton D F, Boyle J, Partington M, Hackett A, Field M, Skinner C, Stevenson R E, Bobrow M, Turner G, Schwartz C E, Gecz J, Raymond F L, Futreal P A, Stratton M R (2009). A systematic, large-scale resequencing screen of X-chromosome coding exons in mental retardation. Nat Genet, 41(5): 535–543PubMedCrossRefGoogle Scholar
  101. Tavares G A, Panepucci E H, Brunger A T (2001). Structural characterization of the intramolecular interaction between the SH3 and guanylate kinase domains of PSD-95. Mol Cell, 8(6): 1313–1325PubMedCrossRefGoogle Scholar
  102. te Velthuis A J, Admiraal J F, Bagowski C P (2007). Molecular evolution of the MAGUK family in metazoan genomes. BMC Evol Biol, 7(1): 129CrossRefGoogle Scholar
  103. Valdar W S (2002). Scoring residue conservation. Proteins, 48(2): 227–241PubMedCrossRefGoogle Scholar
  104. Van Petegem F, Clark K A, Chatelain F C, Minor D L Jr (2004). Structure of a complex between a voltage-gated calcium channel beta-subunit and an alpha-subunit domain. Nature, 429(6992): 671–675PubMedCrossRefGoogle Scholar
  105. Wang C K, Pan L, Chen J, Zhang M (2010). Extensions of PDZ domains as important structural and functional elements. Protein Cell, 1(8): 737–751PubMedCrossRefGoogle Scholar
  106. Wang G S, Hong C J, Yen T Y, Huang H Y, Ou Y, Huang T N, Jung W G, Kuo T Y, Sheng M, Wang T F, Hsueh Y P (2004). Transcriptional modification by a CASK-interacting nucleosome assembly protein. Neuron, 42(1): 113–128PubMedCrossRefGoogle Scholar
  107. Wei Z, Zheng S, Spangler S A, Yu C, Hoogenraad C C, Zhang M (2011). Liprin-mediated large signaling complex organization revealed by the liprin-α/CASK and liprin-α/liprin-β complex structures. Mol Cell, 43(4): 586–598PubMedCrossRefGoogle Scholar
  108. Welch J M, Lu J, Rodriguiz RM, Trotta N C, Peca J, Ding J D, Feliciano C, Chen M, Adams J P, Luo J, Dudek SM, Weinberg R J, Calakos N, Wetsel W C, Feng G (2007). Cortico-striatal synaptic defects and OCD-like behaviours in Sapap3-mutant mice. Nature, 448(7156): 894–900PubMedCrossRefGoogle Scholar
  109. Woods D F, Bryant P J (1991). The discs-large tumor suppressor gene of Drosophila encodes a guanylate kinase homolog localized at septate junctions. Cell, 66(3): 451–464PubMedCrossRefGoogle Scholar
  110. Woods D F, Bryant P J (1993). ZO-1, DlgA and PSD-95/SAP90: homologous proteins in tight, septate and synaptic cell junctions. Mech Dev, 44(2–3): 85–89PubMedCrossRefGoogle Scholar
  111. Woods D F, Hough C, Peel D, Callaini G, Bryant P J (1996). Dlg protein is required for junction structure, cell polarity, and proliferation control in Drosophila epithelia. J Cell Biol, 134(6): 1469–1482PubMedCrossRefGoogle Scholar
  112. Wu H, Feng W, Chen J, Chan L N, Huang S, Zhang M (2007). PDZ domains of Par-3 as potential phosphoinositide signaling integrators. Mol Cell, 28(5): 886–898PubMedCrossRefGoogle Scholar
  113. Yaffe M B, Elia A E (2001). Phosphoserine/threonine-binding domains. Curr Opin Cell Biol, 13(2): 131–138PubMedCrossRefGoogle Scholar
  114. Yu H, Chen J K, Feng S, Dalgarno D C, Brauer A W, Schreiber S L (1994). Structural basis for the binding of proline-rich peptides to SH3 domains. Cell, 76(5): 933–945PubMedCrossRefGoogle Scholar
  115. Zhang J, Yang X, Wang Z, Zhou H, Xie X, Shen Y, Long J (2012). Structure of an l27 domain heterotrimer from cell polarity complex patj/pals1/mals2 reveals mutually independent l27 domain assembly mode. J Biol Chem, 287(14): 11132–11140PubMedCrossRefGoogle Scholar
  116. Zhang M, Wang W (2003). Organization of signaling complexes by PDZ-domain scaffold proteins. Acc Chem Res, 36(7): 530–538PubMedCrossRefGoogle Scholar
  117. Zhang Y, Luan Z, Liu A, Hu G (2001). The scaffolding protein CASK mediates the interaction between rabphilin3a and beta-neurexins. FEBS Lett, 497(2–3): 99–102PubMedCrossRefGoogle Scholar
  118. Zheng C Y, Seabold G K, Horak M, Petralia R S (2011). MAGUKs, synaptic development, and synaptic plasticity. Neuroscientist, 17(5): 493–512PubMedCrossRefGoogle Scholar
  119. Zheng Z, Zhu H, Wan Q, Liu J, Xiao Z, Siderovski D P, Du Q (2010). LGN regulates mitotic spindle orientation during epithelial morphogenesis. J Cell Biol, 189(2): 275–288PubMedCrossRefGoogle Scholar
  120. Zhu J, Shang Y, Xia C, Wang W, Wen W, Zhang M (2011a). Guanylate kinase domains of the MAGUK family scaffold proteins as specific phospho-protein-binding modules. EMBO J, 30(24): 4986–4997PubMedCrossRefGoogle Scholar
  121. Zhu J, Wen W, Zheng Z, Shang Y, Wei Z, Xiao Z, Pan Z, Du Q, Wang W, Zhang M (2011b). LGN/mInsc and LGN/NuMA complex structures suggest distinct functions in asymmetric cell division for the Par3/mInsc/LGN and Gαi/LGN/NuMA pathways. Mol Cell, 43(3): 418–431PubMedCrossRefGoogle Scholar
  122. Züchner S, Wendland J R, Ashley-Koch A E, Collins A L, Tran-Viet K N, Quinn K, Timpano K C, Cuccaro M L, Pericak-Vance M A, Steffens D C, Krishnan K R, Feng G, Murphy D L (2009). Multiple rare SAPAP3 missense variants in trichotillomania and OCD. Mol Psychiatry, 14(1): 6–9PubMedCrossRefGoogle Scholar

Copyright information

© Higher Education Press and Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Jinwei Zhu
    • 1
  • Yuan Shang
    • 1
  • Jia Chen
    • 1
  • Mingjie Zhang
    • 1
    • 2
    Email author
  1. 1.Division of Life Science, State Key Laboratory of Molecular NeuroscienceHong Kong University of Science and TechnologyHong KongChina
  2. 2.Institute for Advanced StudyHong Kong University of Science and TechnologyHong KongChina

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