Plexin A Is a Neuronal Semaphorin Receptor that Controls Axon Guidance

Winberg, Margaret L.; Noordermeer, Jasprina N.; Tamagnone, Luca; Comoglio, Paolo M.; Spriggs, Melanie K.; Tessier‐Lavigne, Marc; Goodman, Corey S.

doi:10.1016/s0092-8674(00)81715-8

Cited by 436 publications

(388 citation statements)

References 40 publications

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“…Members of this family have been implicated in the development of axonal projections and in neural regeneration. [37][38][39] Plexins heterodimerize with members of the neuropilin (NRP) family to form receptors for the semaphorin family of secreted axonal chemorepellants. 40,41 Specifically, PLXNA2 heterodimerizes with either NRP1 or 2 and forms a functional receptor for the class 3 semaphorins.…”

Section: Discussionmentioning

confidence: 99%

Identification of the semaphorin receptor PLXNA2 as a candidate for susceptibility to schizophrenia

et al. 2006

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The discovery of genetic factors that contribute to schizophrenia susceptibility is a key challenge in understanding the etiology of this disease. Here, we report the identification of a novel schizophrenia candidate gene on chromosome 1q32, plexin A2 (PLXNA2), in a genomewide association study using 320 patients with schizophrenia of European descent and 325 matched controls. Over 25 000 single-nucleotide polymorphisms (SNPs) located within approximately 14 000 genes were tested. Out of 62 markers found to be associated with disease status, the most consistent finding was observed for a candidate locus on chromosome 1q32. The marker SNP rs752016 showed suggestive association with schizophrenia (odds ratio (OR) = 1.49, P = 0.006). This result was confirmed in an independent casecontrol sample of European Americans (combined OR = 1.38, P = 0.035) and similar genetic effects were observed in smaller subsets of Latin Americans (OR = 1.26) and Asian Americans (OR = 1.37). Supporting evidence was also obtained from two family-based collections, one of which reached statistical significance (OR = 2.2, P = 0.02). High-density SNP mapping showed that the region of association spans approximately 60 kb of the PLXNA2 gene. Eight out of 14 SNPs genotyped showed statistically significant differences between cases and controls. These results are in accordance with previous genetic findings that identified chromosome 1q32 as a candidate region for schizophrenia. PLXNA2 is a member of the transmembrane semaphorin receptor family that is involved in axonal guidance during development and may modulate neuronal plasticity and regeneration. The PLXNA2 ligand semaphorin 3A has been shown to be upregulated in the cerebellum of individuals with schizophrenia. These observations, together with the genetic results, make PLXNA2 a likely candidate for the 1q32 schizophrenia susceptibility locus.

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Section: Discussionmentioning

confidence: 99%

Identification of the semaphorin receptor PLXNA2 as a candidate for susceptibility to schizophrenia

et al. 2006

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“…Most membrane-bound semaphorins directly bind plexins, whereas class III semaphorins require NPs as obligate coreceptors. [24][25][26] However, recent reports have suggested that semaphorin receptor usage is more complex than previously thought. For example, Sema3E signals independently of NPs through plexin-D1, 16 while Sema7A uses integrins to exert its functions in both the nervous and immune systems.…”

Section: Semaphorins and Their Receptorsmentioning

confidence: 99%

Regulation of immune cell responses by semaphorins and their receptors

2010

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Semaphorins were originally identified as axon guidance factors involved in the development of the neuronal system. However, accumulating evidence indicates that several members of semaphorins, so-called 'immune semaphorins', are crucially involved in various phases of immune responses. These semaphorins regulate both immune cell interactions and immune cell trafficking during physiological and pathological immune responses. Here, we review the following two functional aspects of semaphorins and their receptors in immune responses: their functions in cell-cell interactions and their involvement in immune cell trafficking.

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“…Class 5 semaphorins exist both in vertebrate and invertebrate species ( Figure 2). All semaphorins share a highly conserved 500 amino-acid motif, the semaphorin domain that is also present in other proteins (Winberg et al 10 and Gherardi et al 11 ; see below).…”

Section: Semaphorins and Their Receptorsmentioning

confidence: 99%

The brain within the tumor: new roles for axon guidance molecules in cancers

2005

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Slits, semaphorins and netrins are three families of proteins that can attract or repel growing axons and migrating neurons in the developing nervous system of vertebrates and invertebrates. Recent studies have shown that they are widely expressed outside the nervous system and that they may play important roles in cancers. Several of the genes encoding these proteins are localized on chromosomal region associated with frequent loss-of-heterozygosity in tumors and cancer cell lines and there is also significant hypermethylation of their promoter suggesting that they may act as tumor suppressors. In addition, proteins in all these families and their receptors appear to control the vascularization of the tumors. Last, many axon guidance molecules also regulate cell migration and apoptosis in normal and tumorigenic tissues. Overall, this suggests that molecules that could mimick or block the activity of axon guidance molecules may be used as therapeutic agents for the treatment of malignancy.

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Plexin A Is a Neuronal Semaphorin Receptor that Controls Axon Guidance

Cited by 436 publications

References 40 publications

Identification of the semaphorin receptor PLXNA2 as a candidate for susceptibility to schizophrenia

Identification of the semaphorin receptor PLXNA2 as a candidate for susceptibility to schizophrenia

Regulation of immune cell responses by semaphorins and their receptors

The brain within the tumor: new roles for axon guidance molecules in cancers

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