title: A tripartite protein complex with the potential to couple synaptic vesicle exocytosis to cell adhesion in brain.
abstract: We identify a complex of three proteins in brain that has the potential to couple synaptic vesicle exocytosis to neuronal cell adhesion. The three proteins are: (1) CASK, a protein related to MAGUKs (membrane-associated guanylate kinases); (2) Mint1, a putative vesicular trafficking protein; and (3) Veli1, -2, and -3, vertebrate homologs of C. elegans LIN-7. CASK, Mint1, and Velis form a tight, salt-resistant complex that can be readily isolated. CASK, Mint1, and Velis contain PDZ domains in addition to other modules. However, no PDZ domains are involved in complex formation, leaving them free to recruit cell adhesion molecules, receptors, and channels to the complex. We propose that the tripartite complex acts as a nucleation site for the assembly of proteins involved in synaptic vesicle exocytosis and synaptic junctions.
authors.affiliation: Center for Basic Neuroscience, Department of Molecular Genetics, Howard Hughes Medical Institute, The University of Texas Southwestern Medical Center at Dallas, 75235, USA.
authors.forename: S
authors.initials: S
authors.lastname: Butz
authors.forename: M
authors.initials: M
authors.lastname: Okamoto
authors.forename: T C
authors.initials: TC
authors.lastname: Südhof
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001923:Brain Chemistry / Q000502:physiology*; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins; D002135:Calcium-Binding Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D003001:Cloning, Molecular; D005089:Exocytosis / Q000502:physiology*; D006023:Glycoproteins; D051528:Guanylate Kinases; D015801:Helminth Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins / Q000032:analysis; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000737:chemistry / Q000166:cytology* / Q000502:physiology; D009479:Neuropeptides; D009703:Nucleoside-Phosphate Kinase / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D051381:Rats; D017386:Sequence Homology, Amino Acid; D013572:Synaptic Vesicles / Q000737:chemistry / Q000502:physiology*; D016708:Synaptophysin / Q000032:analysis; D050857:Synaptotagmins; D025521:Tumor Suppressor Proteins; D033921:Vesicular Transport Proteins
chemical_list: C079091:APBA1 protein, human; D048868:Adaptor Proteins, Signal Transducing; C513072:Apba1 protein, mouse; C513071:Apba1 protein, rat; D029742:Caenorhabditis elegans Proteins; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D006023:Glycoproteins; D015801:Helminth Proteins; C099173:LIN-7 protein, C elegans; C114671:LIN7B protein, human; C114670:Lin7a protein, mouse; C485432:Lin7b protein, mouse; C114672:Lin7c protein, mouse; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D016708:Synaptophysin; D025521:Tumor Suppressor Proteins; D033921:Vesicular Transport Proteins; C112162:neurexophilin; D050857:Synaptotagmins; C086959:neurexin Ibeta; C106868:CASK kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D009703:Nucleoside-Phosphate Kinase; C496468:DLG2 protein, human; D051528:Guanylate Kinases