Neurexins: three genes and 1001 products.

The human brain has approximately 10(12) neurons, three orders of magnitude more than there are basepairs in the human genome. Each neuron is connected to other neurons by thousands of synapses, creating a dense network of communicating neurons. Cell-recognition events between neurons at, and outside of synapses, are likely to guide the development and maintenance of the complex network formed by neurons. However, little is known about which proteins are important for neuronal cell recognition. Neurexins, a family of polymorphic cell-surface proteins, might mediate some of these cell recognition events. Thousands of neurexin isoforms are generated from three genes by usage of alternative promoters and alternative splicing. These isoforms are displayed on the neuronal cell surface, with different classes of neurons expressing distinct combinations of isoforms. Neurexins probably have a multitude of ligands, some of which interact only with subsets of neurexin isoforms. This review describes the properties of the neurexin protein family and their potential roles in neuronal cell adhesion and intercellular signaling.

[1]  Kendal Broadie,et al.  Gliotactin, a novel transmembrane protein on peripheral glia, is required to form the blood-nerve barrier in drosophila , 1995, Cell.

[2]  J. Meldolesi,et al.  α-Latrotoxin and related toxins , 1989 .

[3]  J. Sanes,et al.  Molecular Cloning of a Novel Laminin Chain, α5, and Widespread Expression in Adult Mouse Tissues (*) , 1995, The Journal of Biological Chemistry.

[4]  F. Pope,et al.  The complete cDNA sequence of laminin alpha 4 and its relationship to the other human laminin alpha chains. , 1996, European journal of biochemistry.

[5]  T. Südhof,et al.  Structures, Alternative Splicing, and Neurexin Binding of Multiple Neuroligins (*) , 1996, The Journal of Biological Chemistry.

[6]  Y. Jan,et al.  Clustering of Shaker-type K+ channels by interaction with a family of membrane-associated guanylate kinases , 1995, Nature.

[7]  MB Kennedy,et al.  PSD-95 is associated with the postsynaptic density and not with the presynaptic membrane at forebrain synapses , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[8]  D. Noonan,et al.  The complete sequence of perlecan, a basement membrane heparan sulfate proteoglycan, reveals extensive similarity with laminin A chain, low density lipoprotein-receptor, and the neural cell adhesion molecule. , 1991, The Journal of biological chemistry.

[9]  J. Schlessinger,et al.  Identification of a novel contactin‐associated transmembrane receptor with multiple domains implicated in protein–protein interactions , 1997, The EMBO journal.

[10]  T. Südhof,et al.  Neurexins: synaptic cell surface proteins related to the alpha-latrotoxin receptor and laminin. , 1992, Science.

[11]  A. Skubitz,et al.  A synthetic peptide derived from the carboxy terminus of the laminin A chain represents a binding site for the alpha 3 beta 1 integrin , 1992, The Journal of cell biology.

[12]  T. Südhof,et al.  High Affinity Binding of α-Latrotoxin to Recombinant Neurexin Iα (*) , 1995, The Journal of Biological Chemistry.

[13]  T. Südhof,et al.  Cartography of neurexins: More than 1000 isoforms generated by alternative splicing and expressed in distinct subsets of neurons , 1995, Neuron.

[14]  T. Südhof,et al.  Structure and Evolution of Neurexophilin , 1996, The Journal of Neuroscience.

[15]  J. Prince,et al.  The primary structure of NG2, a novel membrane-spanning proteoglycan , 1991, The Journal of cell biology.

[16]  T. Südhof,et al.  Neuroligin 1: A splice site-specific ligand for β-neurexins , 1995, Cell.

[17]  S. K. Kim,et al.  The C. elegans vulval induction gene lin-2 encodes a member of the MAGUK family of cell junction proteins. , 1996, Development.

[18]  P. Seeburg,et al.  Domain interaction between NMDA receptor subunits and the postsynaptic density protein PSD-95. , 1995, Science.

[19]  T. Südhof,et al.  Conserved domain structure of beta-neurexins. Unusual cleaved signal sequences in receptor-like neuronal cell-surface proteins. , 1994, The Journal of biological chemistry.

[20]  U. Tepass,et al.  crumbs encodes an EGF-like protein expressed on apical membranes of Drosophila epithelial cells and required for organization of epithelia , 1990, Cell.

[21]  R. Deutzmann,et al.  Structural study of long arm fragments of laminin. Evidence for repetitive C-terminal sequences in the A-chain, not present in the B-chains. , 1988, European journal of biochemistry.

[22]  T. Südhof,et al.  Polypeptide composition of the alpha-latrotoxin receptor. High affinity binding protein consists of a family of related high molecular weight polypeptides complexed to a low molecular weight protein. , 1993, The Journal of biological chemistry.

[23]  G. R. Dodge,et al.  Primary structure of the human heparan sulfate proteoglycan from basement membrane (HSPG2/perlecan). A chimeric molecule with multiple domains homologous to the low density lipoprotein receptor, laminin, neural cell adhesion molecules, and epidermal growth factor. , 1992, The Journal of biological chemistry.

[24]  M. Baker,et al.  Sex hormone‐binding globulin, androgen‐binding protein, and vitamin K‐dependent protein S are homologous to laminin A, merosin, and Drosophila crumbs protein , 1992, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[25]  T. Uemura,et al.  A Drosophila homolog of cadherin associated with armadillo and essential for embryonic cell-cell adhesion. , 1994, Developmental biology.

[26]  R. Poulsom,et al.  Molecular cloning and tissue expression of FAT, the human homologue of the Drosophila fat gene that is located on chromosome 4q34-q35 and encodes a putative adhesion molecule. , 1995, Genomics.

[27]  Andreas Prokop,et al.  A Drosophila Neurexin Is Required for Septate Junction and Blood-Nerve Barrier Formation and Function , 1996, Cell.

[28]  J. Rothberg,et al.  slit: an extracellular protein necessary for development of midline glia and commissural axon pathways contains both EGF and LRR domains. , 1990, Genes & development.

[29]  T. Südhof,et al.  CASK: a novel dlg/PSD95 homolog with an N-terminal calmodulin-dependent protein kinase domain identified by interaction with neurexins , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[30]  R. Scheller,et al.  The ability of agrin to cluster AChRs depends on alternative splicing and on cell surface proteoglycans , 1993, Neuron.

[31]  R. Ruben,et al.  Distribution of microtubules and microfilaments in developing vestibular sensory epithelium of mouse otocysts grown in vitro. , 1975, Journal of cell science.

[32]  J. R. Martin,et al.  A new Drosophila Ca2+/calmodulin‐dependent protein kinase (Caki) is localized in the central nervous system and implicated in walking speed. , 1996, The EMBO journal.

[33]  T. Südhof,et al.  Binding of neuroligins to PSD-95. , 1997, Science.

[34]  M. Sheng,et al.  PDZs and Receptor/Channel Clustering: Rounding Up the Latest Suspects , 1996, Neuron.

[35]  S. K. Kim,et al.  Tight junctions, membrane-associated guanylate kinases and cell signaling. , 1995, Current opinion in cell biology.

[36]  T. Südhof,et al.  Binding Properties of Neuroligin 1 and Neurexin 1β Reveal Function as Heterophilic Cell Adhesion Molecules* , 1997, The Journal of Biological Chemistry.

[37]  N. Patel,et al.  Drosophila neurotactin, a surface glycoprotein with homology to serine esterases, is dynamically expressed during embryogenesis. , 1990, Development.

[38]  S. Carlson,et al.  Neurexin Is Expressed on Nerves, But Not at Nerve Terminals, in the Electric Organ , 1997, The Journal of Neuroscience.

[39]  O. Shamotienko,et al.  Isolation and Biochemical Characterization of a Ca2+-independent α-Latrotoxin-binding Protein* , 1996, The Journal of Biological Chemistry.

[40]  John H. Lewis,et al.  Crystal Structures of a Complexed and Peptide-Free Membrane Protein–Binding Domain: Molecular Basis of Peptide Recognition by PDZ , 1996, Cell.

[41]  C. Schneider,et al.  The protein encoded by a growth arrest-specific gene (gas6) is a new member of the vitamin K-dependent proteins related to protein S, a negative coregulator in the blood coagulation cascade , 1993, Molecular and cellular biology.

[42]  J. Schlessinger,et al.  Close Similarity between Drosophila Neurexin IV and Mammalian Caspr Protein Suggests a Conserved Mechanism for Cellular Interactions , 1997, Cell.