Neuropilin-1

Definition:

Cell-surface receptor involved in the development of the cardiovascular system, in angiogenesis, in the formation of certain neuronal circuits and in organogenesis outside the nervous system. Mediates the chemorepulsant activity of semaphorins. Recognizes a C-end rule (CendR) motif R/KXXR/K on its ligands which causes cellular internalization and vascular leakage. It binds to semaphorin 3A, the PLGF-2 isoform of PGF, the VEGF165 isoform of VEGFA and VEGFB. Coexpression with KDR results in increased VEGF165 binding to KDR as well as increased chemotaxis. Regulates VEGF-induced angiogenesis. Binding to VEGFA initiates a signaling pathway needed for motor neuron axon guidance and cell body migration, including for the caudal migration of facial motor neurons from rhombomere 4 to rhombomere 6 during embryonic development (By similarity). Regulates mitochondrial iron transport via interaction with ABCB8/MITOSUR.; (Microbial infection) Acts as a host factor for human coronavirus SARS-CoV-2 infection. Recognizes and binds to CendR motif RRAR on SARS-CoV-2 spike protein S1 which enhances SARS-CoV-2 infection.; [Isoform 2]: Binds VEGF-165 and may inhibit its binding to cells. May induce apoptosis by sequestering VEGF-165. May bind as well various members of the semaphorin family. Its expression has an averse effect on blood vessel number and integrity.

References:

[1]. Z He, et al. Neuropilin is a receptor for the axonal chemorepellent Semaphorin III. Cell. 1997 Aug 22;90(4):739-51. [Content Brief]

[2]. James L Daly, et al. Neuropilin-1 is a host factor for SARS-CoV-2 infection. Science. 2020 Nov 13;370(6518):861-865. [Content Brief]

[3]. Ludovico Cantuti-Castelvetri, et al. Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity. Science. 2020 Nov 13;370(6518):856-860. [Content Brief]

[4]. Weiwei He, et al. CMT2D neuropathy is linked to the neomorphic binding activity of glycyl-tRNA synthetase. Nature. 2015 Oct 29;526(7575):710-4. [Content Brief]

[5]. Tambet Teesalu, et al. C-end rule peptides mediate neuropilin-1-dependent cell, vascular, and tissue penetration. Proc Natl Acad Sci U S A. 2009 Sep 22;106(38):16157-62. [Content Brief]

[6]. Theo Issitt, et al. Neuropilin-1 Controls Endothelial Homeostasis by Regulating Mitochondrial Function and Iron-Dependent Oxidative Stress. iScience. 2019 Jan 25;11:205-223. [Content Brief]

[7]. S Soker, et al. Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor. Cell. 1998 Mar 20;92(6):735-45. [Content Brief]

[8]. Z Gluzman-Poltorak, et al. Neuropilin-2 is a receptor for the vascular endothelial growth factor (VEGF) forms VEGF-145 and VEGF-165 [corrected]. J Biol Chem. 2000 Jun 16;275(24):18040-5. [Content Brief]

[9]. M L Gagnon, et al. Identification of a natural soluble neuropilin-1 that binds vascular endothelial growth factor: In vivo expression and antitumor activity. Proc Natl Acad Sci U S A. 2000 Mar 14;97(6):2573-8. [Content Brief]

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