Adhesion molecules in the nervous system: structural insights into function and diversity.

The unparalleled complexity of intercellular connections in the nervous system presents requirements for high levels of both specificity and diversity for the proteins that mediate cell adhesion. Here we describe recent advances toward understanding the molecular mechanisms that underlie adhesive binding, specificity, and diversity for several well-characterized families of adhesion molecules in the nervous system. Although many families of adhesion proteins, including cadherins and immunoglobulin superfamily members, are utilized in neural and nonneural contexts, nervous system-specific diversification mechanisms, such as precisely regulated alternative splicing, provide an important means to enable their function in the complex context of the nervous system.

[1]  Fabiana Bahna,et al.  Type II Cadherin Ectodomain Structures: Implications for Classical Cadherin Specificity , 2006, Cell.

[2]  M. Jensen,et al.  Interfacial tryptophan residues: a role for the cation-pi effect? , 2005, Biophysical journal.

[3]  L. Shapiro,et al.  ADAM and Eph: How Ephrin-Signaling Cells Become Detached , 2005, Cell.

[4]  C. Blobel,et al.  Adam Meets Eph: An ADAM Substrate Recognition Module Acts as a Molecular Switch for Ephrin Cleavage In trans , 2005, Cell.

[5]  Thomas C. Südhof,et al.  A Splice Code for trans-Synaptic Cell Adhesion Mediated by Binding of Neuroligin 1 to α- and β-Neurexins , 2005, Neuron.

[6]  M. Arnaout,et al.  Integrin structure, allostery, and bidirectional signaling. , 2005, Annual review of cell and developmental biology.

[7]  M. Kondo,et al.  Extensive Diversity of Ig-Superfamily Proteins in the Immune System of Insects , 2005, Science.

[8]  E. Peles,et al.  Gliomedin Mediates Schwann Cell-Axon Interaction and the Molecular Assembly of the Nodes of Ranvier , 2005, Neuron.

[9]  Lawrence Shapiro,et al.  Specificity of cell-cell adhesion by classical cadherins: Critical role for low-affinity dimerization through beta-strand swapping. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[10]  F. Liao,et al.  Identification of a transiently exposed VE-cadherin epitope that allows for specific targeting of an antibody to the tumor neovasculature. , 2005, Blood.

[11]  Yuedong Yang,et al.  Solution Structure of AF-6 PDZ Domain and Its Interaction with the C-terminal Peptides from Neurexin and Bcr* , 2005, Journal of Biological Chemistry.

[12]  L. G. Moss,et al.  The zebrafish down syndrome cell adhesion molecule is involved in cell movement during embryogenesis. , 2005, Developmental biology.

[13]  P. Scheiffele,et al.  Control of Excitatory and Inhibitory Synapse Formation by Neuroligins , 2005, Science.

[14]  J. Hell,et al.  Thrombospondins Are Astrocyte-Secreted Proteins that Promote CNS Synaptogenesis , 2005, Cell.

[15]  C. Redies,et al.  Selective synaptic cadherin expression by traced neurons of the chicken visual system 1 1 Supplementary data associated with this article can be found at doi:10.1016/j.neuroscience.2004.05.023. , 2004, Neuroscience.

[16]  Ioan Andricioaei,et al.  Conversion between three conformational states of integrin I domains with a C-terminal pull spring studied with molecular dynamics. , 2004, Structure.

[17]  E. Evans,et al.  Trans-bonded pairs of E-cadherin exhibit a remarkable hierarchy of mechanical strengths. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[18]  Barry S. Coller,et al.  Structural basis for allostery in integrins and binding to fibrinogen-mimetic therapeutics , 2004, Nature.

[19]  G. Landreth,et al.  Microglial Phagocytosis of Fibrillar β-Amyloid through a β1 Integrin-Dependent Mechanism , 2004, The Journal of Neuroscience.

[20]  K. Schulten,et al.  Structural insights into how the MIDAS ion stabilizes integrin binding to an RGD peptide under force. , 2004, Structure.

[21]  T. Yagi,et al.  Genomic organization and transcripts of the zebrafish Protocadherin genes. , 2004, Gene.

[22]  J. Hardin,et al.  Skin tight: cell adhesion in the epidermis of Caenorhabditis elegans. , 2004, Current opinion in cell biology.

[23]  S. Pfaff,et al.  β1 Integrins in Muscle, But Not in Motor Neurons, Are Required for Skeletal Muscle Innervation , 2004, The Journal of Neuroscience.

[24]  J. C. Clemens,et al.  Alternative Splicing of Drosophila Dscam Generates Axon Guidance Receptors that Exhibit Isoform-Specific Homophilic Binding , 2004, Cell.

[25]  J. Sanes,et al.  Axon fasciculation defects and retinal dysplasias in mice lacking the immunoglobulin superfamily adhesion molecule BEN/ALCAM/SC1 , 2004, Molecular and Cellular Neuroscience.

[26]  S. Grzesiek,et al.  Proteolytic E‐cadherin activation followed by solution NMR and X‐ray crystallography , 2004, The EMBO journal.

[27]  J. Hardin,et al.  Sticky worms: adhesion complexes in C. elegans , 2004, Journal of Cell Science.

[28]  J. Hardin,et al.  Cell adhesion receptors in C. elegans , 2004, Journal of Cell Science.

[29]  C. Redies,et al.  Internal structure of the nucleus rotundus revealed by mapping cadherin expression in the embryonic chicken visual system , 2003, The Journal of comparative neurology.

[30]  C. Chothia,et al.  The immunoglobulin superfamily in Drosophila melanogaster and Caenorhabditis elegans and the evolution of complexity , 2003, Development.

[31]  O. Hobert,et al.  New insights into the diversity and function of neuronal immunoglobulin superfamily molecules. , 2003, Annual review of neuroscience.

[32]  David L Stokes,et al.  Untangling Desmosomal Knots with Electron Tomography , 2003, Science.

[33]  J. Sanes,et al.  Synaptic adhesion molecules. , 2003, Current opinion in cell biology.

[34]  Wei Yang,et al.  Small molecule integrin antagonists that bind to the beta2 subunit I-like domain and activate signals in one direction and block them in the other. , 2003, Immunity.

[35]  J. Haspel,et al.  The L1CAM extracellular region: a multi-domain protein with modular and cooperative binding modes. , 2003, Frontiers in bioscience : a journal and virtual library.

[36]  T. Südhof,et al.  α-Neurexins couple Ca2+ channels to synaptic vesicle exocytosis , 2003, Nature.

[37]  Thomas Bourgeron,et al.  Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism , 2003, Nature Genetics.

[38]  M. Humphries,et al.  Mapping functional residues onto integrin crystal structures. , 2003, Current opinion in structural biology.

[39]  M. Missler Synaptic cell adhesion goes functional , 2003, Trends in Neurosciences.

[40]  C. Redies,et al.  Cadherins as regulators for the emergence of neural nets from embryonic divisions , 2003, Journal of Physiology-Paris.

[41]  T. Yagi Diversity of the cadherin‐related neuronal receptor/protocadherin family and possible DNA rearrangement in the brain , 2003, Genes to cells : devoted to molecular & cellular mechanisms.

[42]  D. Benson,et al.  Identification and localization of multiple classic cadherins in developing rat limbic system , 2002, Neuroscience.

[43]  C. ffrench-Constant,et al.  CNS integrins switch growth factor signalling to promote target-dependent survival , 2002, Nature Cell Biology.

[44]  C. Redies,et al.  Targeting Axons to Specific Fiber Tracts In Vivoby Altering Cadherin Expression , 2002, The Journal of Neuroscience.

[45]  Junichi Takagi,et al.  Integrin activation and structural rearrangement , 2002, Immunological reviews.

[46]  Tom Maniatis,et al.  Promoter Choice Determines Splice Site Selection in Protocadherin α and γ Pre-mRNA Splicing , 2002 .

[47]  Pierre Bongrand,et al.  Fast dissociation kinetics between individual E‐cadherin fragments revealed by flow chamber analysis , 2002, The EMBO journal.

[48]  T. Südhof,et al.  Structure and evolution of neurexin genes: insight into the mechanism of alternative splicing. , 2002, Genomics.

[49]  T. Jessell,et al.  Regulation of Motor Neuron Pool Sorting by Differential Expression of Type II Cadherins , 2002, Cell.

[50]  T. Boggon,et al.  C-Cadherin Ectodomain Structure and Implications for Cell Adhesion Mechanisms , 2002, Science.

[51]  C. ffrench-Constant,et al.  The oligodendrocyte precursor mitogen PDGF stimulates proliferation by activation of αvβ3 integrins , 2002 .

[52]  Martin Lackmann,et al.  Crystal structure of an Eph receptor–ephrin complex , 2001, Nature.

[53]  David R. Colman,et al.  Molecules, maps and synapse specificity , 2001, Nature Reviews Neuroscience.

[54]  C. Redies,et al.  Expression of R-cadherin and N-cadherin by cell groups and fiber tracts in the developing mouse forebrain: relation to the formation of functional circuits , 2001, Neuroscience.

[55]  Thilo Stehle,et al.  Crystal Structure of the Extracellular Segment of Integrin αVβ3 , 2001, Science.

[56]  J. Pierce,et al.  Dentate hilar mossy cells and somatostatin-containing neurons are immunoreactive for the α8 integrin subunit: characterization in normal and kainic acid-treated rats , 2001, Neuroscience.

[57]  H. Erickson,et al.  Cell adhesion molecule L1 in folded (horseshoe) and extended conformations. , 2001, Molecular biology of the cell.

[58]  Hugo J. Bellen,et al.  Axon-Glia Interactions and the Domain Organization of Myelinated Axons Requires Neurexin IV/Caspr/Paranodin , 2001, Neuron.

[59]  Elior Peles,et al.  Contactin Orchestrates Assembly of the Septate-like Junctions at the Paranode in Myelinated Peripheral Nerve , 2001, Neuron.

[60]  Stephen J. Kaufman,et al.  Enhanced Expression of the α7β1 Integrin Reduces Muscular Dystrophy and Restores Viability in Dystrophic Mice , 2001, The Journal of cell biology.

[61]  M Dickson,et al.  Comparative DNA sequence analysis of mouse and human protocadherin gene clusters. , 2001, Genome research.

[62]  D. Burkin,et al.  Laminin and alpha7beta1 integrin regulate agrin-induced clustering of acetylcholine receptors. , 2000, Journal of cell science.

[63]  D. DeSimone,et al.  Active Zones on Motor Nerve Terminals Contain α3β1 Integrin , 2000, The Journal of Neuroscience.

[64]  J. C. Clemens,et al.  Drosophila Dscam Is an Axon Guidance Receptor Exhibiting Extraordinary Molecular Diversity , 2000, Cell.

[65]  F. van Roy,et al.  Phylogenetic analysis of the cadherin superfamily allows identification of six major subfamilies besides several solitary members. , 2000, Journal of molecular biology.

[66]  K. Diederichs,et al.  The Crystal Structure of the Ligand Binding Module of Axonin-1/TAG-1 Suggests a Zipper Mechanism for Neural Cell Adhesion , 2000, Cell.

[67]  E. Ginns,et al.  The structure and expression of the human neuroligin-3 gene. , 2000, Gene.

[68]  H. Hutter,et al.  Conservation and novelty in the evolution of cell adhesion and extracellular matrix genes. , 2000, Science.

[69]  David R. Colman,et al.  Molecular Modification of N-Cadherin in Response to Synaptic Activity , 2000, Neuron.

[70]  S. Nishikawa,et al.  Regulation of E- and P-cadherin expression correlated with melanocyte migration and diversification. , 1999, Developmental biology.

[71]  J. Deisenhofer,et al.  Regulation of LNS Domain Function by Alternative Splicing: The Structure of the Ligand-Binding Domain of Neurexin Iβ , 1999, Cell.

[72]  David R. Colman,et al.  The Diversity of Cadherins and Implications for a Synaptic Adhesive Code in the CNS , 1999, Neuron.

[73]  T. Maniatis,et al.  A Striking Organization of a Large Family of Human Neural Cadherin-like Cell Adhesion Genes , 1999, Cell.

[74]  Gerhard Wagner,et al.  Structure of a Heterophilic Adhesion Complex between the Human CD2 and CD58 (LFA-3) Counterreceptors , 1999, Cell.

[75]  D. Benson,et al.  Neural (N)‐cadherin at developing thalamocortical synapses provides an adhesion mechanism for the formation of somatopically organized connections , 1999, The Journal of comparative neurology.

[76]  O. Pertz,et al.  A new crystal structure, Ca2+ dependence and mutational analysis reveal molecular details of E‐cadherin homoassociation , 1999, The EMBO journal.

[77]  T. Südhof,et al.  Neuroligin 1 is a postsynaptic cell-adhesion molecule of excitatory synapses. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[78]  J. Sanes,et al.  Formation of lamina-specific synaptic connections , 1999, Current Opinion in Neurobiology.

[79]  P. Sonderegger,et al.  Neurite Fasciculation Mediated by Complexes of Axonin-1 and Ng Cell Adhesion Molecule , 1998, The Journal of cell biology.

[80]  T. Südhof,et al.  The Making of Neurexins , 1998, Journal of neurochemistry.

[81]  P. Bjorkman,et al.  Crystal structure of hemolin: a horseshoe shape with implications for homophilic adhesion. , 1998, Science.

[82]  M. Takeichi,et al.  Neural crest emigration from the neural tube depends on regulated cadherin expression. , 1998, Development.

[83]  Masahiko Watanabe,et al.  Diversity Revealed by a Novel Family of Cadherins Expressed in Neurons at a Synaptic Complex , 1998, Neuron.

[84]  Wayne A. Hendrickson,et al.  Structure-Function Analysis of Cell Adhesion by Neural (N-) Cadherin , 1998, Neuron.

[85]  C Chothia,et al.  Structural determinants in the sequences of immunoglobulin variable domain. , 1998, Journal of molecular biology.

[86]  M. Bate,et al.  Absence of PS integrins or laminin A affects extracellular adhesion, but not intracellular assembly, of hemiadherens and neuromuscular junctions in Drosophila embryos. , 1998, Developmental biology.

[87]  A. Lesk,et al.  Standard conformations for the canonical structures of immunoglobulins. , 1997, Journal of molecular biology.

[88]  R. Liddington,et al.  The von Willebrand Factor A3 Domain Does Not Contain a Metal Ion-dependent Adhesion Site Motif* , 1997, The Journal of Biological Chemistry.

[89]  K. Yamada,et al.  Integrins can collaborate with growth factors for phosphorylation of receptor tyrosine kinases and MAP kinase activation: roles of integrin aggregation and occupancy of receptors , 1996, The Journal of cell biology.

[90]  T. Brümmendorf,et al.  Structure/function relationships of axon-associated adhesion receptors of the immunoglobulin superfamily , 1996, Current Opinion in Neurobiology.

[91]  R. Liddington,et al.  Ligand Binding to Integrin αIIbβ3 Is Dependent on a MIDAS-like Domain in the β3 Subunit* , 1996, The Journal of Biological Chemistry.

[92]  W. Hendrickson,et al.  Crystal Structure of the Extracellular Domain from P0, the Major Structural Protein of Peripheral Nerve Myelin , 1996, Neuron.

[93]  D. Colman,et al.  A Model for Central Synaptic Junctional Complex Formation Based on the Differential Adhesive Specificities of the Cadherins , 1996, Neuron.

[94]  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.

[95]  M. Ikura,et al.  Structural basis of calcium-induced E-cadherin rigidification and dimerization , 1996, Nature.

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

[97]  M. Seldin,et al.  Protocadherin Pcdh2 shows properties similar to, but distinct from, those of classical cadherins. , 1995, Journal of cell science.

[98]  W. Hendrickson,et al.  Considerations on the folding topology and evolutionary origin of cadherin domains. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

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

[100]  D. Sherman,et al.  Novel E-cadherin-mediated adhesion in peripheral nerve: Schwann cell architecture is stabilized by autotypic adherens junctions [published erratum appears in J Cell Biol 1995 Jun;129(6):1721] , 1995, The Journal of cell biology.

[101]  Peter D. Kwong,et al.  Structural basis of cell-cell adhesion by cadherins , 1995, Nature.

[102]  R. Liddington,et al.  Crystal structure of the A domain from the a subunit of integrin CR3 (CD11 b/CD18) , 1995, Cell.

[103]  M. Ikura,et al.  Solution structure of the epithelial cadherin domain responsible for selective cell adhesion , 1995, Science.

[104]  D. Kirschner,et al.  Mutations in demyelinating peripheral neuropathies support molecular model of myelin PO‐glycoprotein extracellular domain , 1994, Journal of neuroscience research.

[105]  V. Quaranta,et al.  Beta 4 integrin expression in myelinating Schwann cells is polarized, developmentally regulated and axonally dependent. , 1994, Development.

[106]  F. Giancotti,et al.  Axonal regulation of Schwann cell integrin expression suggests a role for alpha 6 beta 4 in myelination , 1993, The Journal of cell biology.

[107]  W A Hendrickson,et al.  Structure of a fibronectin type III domain from tenascin phased by MAD analysis of the selenomethionyl protein. , 1992, Science.

[108]  T. Springer,et al.  The three-dimensional structure of integrins and their ligands, and conformational regulation of cell adhesion. , 2004, Advances in protein chemistry.

[109]  C. Redies,et al.  The cadherin superfamily in neural development: diversity, function and interaction with other molecules. , 2003, Frontiers in bioscience : a journal and virtual library.

[110]  Casimir A. Kulikowski,et al.  Geometric Invariant Core for the CL and CH1 Domains of Immunoglobulin Molecules , 2000, J. Comput. Biol..

[111]  M. Mareel,et al.  Cadherin expression in the eye. , 2000, Bulletin de la Societe belge d'ophtalmologie.

[112]  B. Gumbiner,et al.  Molecular and functional analysis of cadherin-based adherens junctions. , 1997, Annual review of cell and developmental biology.

[113]  J. Sanes,et al.  Lamina-specific cues guide outgrowth and arborization of retinal axons in the optic tectum. , 1995, Development.

[114]  A. F. Williams,et al.  Structural diversity in domains of the immunoglobulin superfamily. , 1989, Cold Spring Harbor symposia on quantitative biology.

[115]  A. F. Williams,et al.  The immunoglobulin superfamily--domains for cell surface recognition. , 1988, Annual review of immunology.