Structural and functional relation of neuropilins.

Neuropilin is a type I transmembrane protein and the molecular mass is 120 kDa. Two homologues, Neuropilin-1 and -2, are identified. The primary structure of Neuropilin-1 and Neuropilin-2 is well conserved and is divided into four domains, CUB (a1/a2) domain, FV/FVIII (b1/b2) domain, MAM (c) domain, and (d) domain that contains a transmembrane and a short cytoplasmic region. Both Neuropilin-1 and Neuropilin-2 have truncated and secreted form of splice variants. Neuropilins act as a receptor for two different extracellular ligands, class 3 semaphorins and specific isoforms of vascular endothelial growth factor. In both cases, neuropilin requires an additional transmembrane molecule to exhibit biological activity. Plexin-A is essential for class 3 semaphorin signaling. Vascular endothelial cell growth factor (VEGF) receptor is the major receptor for VEGF and neuropilin acts as isoform specific co-receptor for VEGF. The CUB and FV/FVIII domains of Neuropilin are the binding sites of semaphorin and VEGF. The MAM domain mediates semaphorin signaling to Plexin-A. Cross talk between semaphorin and VEGF on neuropilin suggests that class 3 semaphorins and the secreted forms of neuropilin act as antagonists to VEGF and its related growth factors.

[1]  Alex L Kolodkin,et al.  Neuropilin Is a Semaphorin III Receptor , 1997, Cell.

[2]  M. Tessier-Lavigne,et al.  Neuropilin Is a Receptor for the Axonal Chemorepellent Semaphorin III , 1997, Cell.

[3]  Alex L Kolodkin,et al.  Neuropilin-2 Is a Receptor for Semaphorin IV Insight into the Structural Basis of Receptor Function and Specificity , 1998, Neuron.

[4]  R. Kalb,et al.  Molecular basis of semaphorin-mediated axon guidance. , 2000, Journal of neurobiology.

[5]  H. Fujisawa,et al.  Determination of Cell Adhesion Sites of Neuropilin-1 , 2000, The Journal of cell biology.

[6]  C. Goodman,et al.  Plexin A Is a Neuronal Semaphorin Receptor that Controls Axon Guidance , 1998, Cell.

[7]  J. V. Moran,et al.  Initial sequencing and analysis of the human genome. , 2001, Nature.

[8]  J. Minna,et al.  Human semaphorins A(V) and IV reside in the 3p21.3 small cell lung cancer deletion region and demonstrate distinct expression patterns. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[9]  Takaaki Ito,et al.  Diverse gene expression and function of semaphorins in developing lung: positive and negative regulatory roles of semaphorins in lung branching morphogenesis , 2001, Genes to cells : devoted to molecular & cellular mechanisms.

[10]  R. Kalb,et al.  Neuropilin-1 Extracellular Domains Mediate Semaphorin D/III-Induced Growth Cone Collapse , 1998, Neuron.

[11]  Shay Soker,et al.  Neuropilin-1 Is Expressed by Endothelial and Tumor Cells as an Isoform-Specific Receptor for Vascular Endothelial Growth Factor , 1998, Cell.

[12]  M. Schachner,et al.  Analysis of the L1-Deficient Mouse Phenotype Reveals Cross-Talk between Sema3A and L1 Signaling Pathways in Axonal Guidance , 2000, Neuron.

[13]  M. Klagsbrun,et al.  Vascular endothelial growth factor and its receptors. , 1996, Cytokine & growth factor reviews.

[14]  B. Eickholt,et al.  Structural Features of Collapsin Required for Biological Activity and Distribution of Binding Sites in the Developing Chick , 1997, Molecular and Cellular Neuroscience.

[15]  C. Goodman,et al.  Neuropilin-2, a Novel Member of the Neuropilin Family, Is a High Affinity Receptor for the Semaphorins Sema E and Sema IV but Not Sema III , 1997, Neuron.

[16]  Zhigang He,et al.  Semaphorin–Neuropilin Interactions Underlying Sympathetic Axon Responses to Class III Semaphorins , 1998, Neuron.

[17]  M. Poo,et al.  Unified Nomenclature for the Semaphorins/Collapsins , 1999, Cell.

[18]  S. Strittmatter,et al.  PlexinA1 Autoinhibition by the Plexin Sema Domain , 2001, Neuron.

[19]  R. Dubose,et al.  A poxvirus-encoded semaphorin induces cytokine production from monocytes and binds to a novel cellular semaphorin receptor, VESPR. , 1998, Immunity.

[20]  M. Lohrum,et al.  The Chemorepulsive Activity of the Axonal Guidance Signal Semaphorin D Requires Dimerization* , 1998, The Journal of Biological Chemistry.

[21]  M. Klagsbrun,et al.  Genomic organization of human neuropilin-1 and neuropilin-2 genes: identification and distribution of splice variants and soluble isoforms. , 2000, Genomics.

[22]  T. Yagi,et al.  Neuropilin–Semaphorin III/D-Mediated Chemorepulsive Signals Play a Crucial Role in Peripheral Nerve Projection in Mice , 1997, Neuron.

[23]  S. Takagi,et al.  Expression of a cell adhesion molecule, neuropilin, in the developing chick nervous system. , 1995, Developmental biology.

[24]  M. Matsumoto,et al.  Identification of CD72 as a lymphocyte receptor for the class IV semaphorin CD100: a novel mechanism for regulating B cell signaling. , 2000, Immunity.

[25]  W. Risau,et al.  Mechanisms of angiogenesis , 1997, Nature.

[26]  J. Bolz,et al.  Semaphorin 3A–Vascular Endothelial Growth Factor-165 Balance Mediates Migration and Apoptosis of Neural Progenitor Cells by the Recruitment of Shared Receptor , 2001, The Journal of Neuroscience.

[27]  S. Soker,et al.  Identification of a natural soluble neuropilin-1 that binds vascular endothelial growth factor: In vivo expression and antitumor activity. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[28]  T. Yagi,et al.  Disruption of Semaphorin III/D Gene Causes Severe Abnormality in Peripheral Nerve Projection , 1997, Neuron.

[29]  H. Cai,et al.  Cloning and Characterization of Neuropilin-1-Interacting Protein: A PSD-95/Dlg/ZO-1 Domain-Containing Protein That Interacts with the Cytoplasmic Domain of Neuropilin-1 , 1999, The Journal of Neuroscience.

[30]  K. Agata,et al.  The A5 antigen, a candidate for the neuronal recognition molecule, has homologies to complement components and coagulation factors , 1991, Neuron.

[31]  M. Tessier-Lavigne,et al.  Plexin-A3 Mediates Semaphorin Signaling and Regulates the Development of Hippocampal Axonal Projections , 2001, Neuron.

[32]  T. Yagi,et al.  A requirement for neuropilin-1 in embryonic vessel formation. , 1999, Development.

[33]  R. Kalb,et al.  Semaphorins A and E act as antagonists of neuropilin-1 and agonists of neuropilin-2 receptors , 1998, Nature Neuroscience.

[34]  R. Kalb,et al.  Plexin-Neuropilin-1 Complexes Form Functional Semaphorin-3A Receptors , 1999, Cell.

[35]  T. Kitsukawa,et al.  Developmentally regulated expression of a cell surface protein, neuropilin, in the mouse nervous system. , 1996, Journal of neurobiology.

[36]  Hiroaki Kobayashi,et al.  Secreted Chick Semaphorins Bind Recombinant Neuropilin with Similar Affinities but Bind Different Subsets of Neurons In Situ , 1997, Neuron.

[37]  T. Kitsukawa,et al.  Overexpression of a membrane protein, neuropilin, in chimeric mice causes anomalies in the cardiovascular system, nervous system and limbs. , 1995, Development.

[38]  G. Zhao,et al.  GIPC, a PDZ domain containing protein, interacts specifically with the C terminus of RGS-GAIP. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[39]  L. Feiner,et al.  A Dominant Negative Receptor for Specific Secreted Semaphorins Is Generated by Deleting an Extracellular Domain from Neuropilin-1 , 1999, The Journal of Neuroscience.

[40]  R. Kalb,et al.  A PDZ Protein Regulates the Distribution of the Transmembrane Semaphorin, M-SemF* , 1999, The Journal of Biological Chemistry.

[41]  B. J. Limberg,et al.  Vascular Endothelial Growth Factor Receptor-2 and Neuropilin-1 Form a Receptor Complex That Is Responsible for the Differential Signaling Potency of VEGF165 and VEGF121 * , 2001, The Journal of Biological Chemistry.

[42]  M. Poo,et al.  Plexins Are a Large Family of Receptors for Transmembrane, Secreted, and GPI-Anchored Semaphorins in Vertebrates , 1999, Cell.

[43]  M. Shibuya,et al.  Vascular Endothelial Growth Factor Receptor-1 and Neuropilin-2 Form Complexes* , 2001, The Journal of Biological Chemistry.