Alternative titles; symbols
HGNC Approved Gene Symbol: PLXNA3
Cytogenetic location: Xq28 Genomic coordinates (GRCh38): X:154,458,281-154,477,779 (from NCBI)
In hunting for unknown genes on the human X chromosome, Maestrini et al. (1996) identified a cDNA in Xq28 encoding a transmembrane protein, which they termed SEX, of 1,871 amino acids. SEX shares significant homology with the extracellular domain of the receptors encoded by the oncogenes MET (164860), RON (600168), and SEA (165110), i.e., the hepatocyte growth factor (HGF) receptor family. Further screening of cDNA libraries identified 3 additional sequences closely related to SEX; they were named SEP (601053), OCT (601054), and NOV (601055), and were located on human chromosomes 3p, 1, and 3q, respectively, by screening a panel of DNAs from hamster/human somatic cell hybrids. The proteins encoded by these genes contain large cytoplasmic domains characterized by a distinctive highly conserved sequence, which they called the SEX domain. Northern blot analysis revealed different expression of the SEX family of genes in fetal tissues, with SEX, OCT, and NOV predominantly expressed in brain, and SEP expressed at highest levels in kidney. In situ hybridization analysis revealed that a mouse SEX homolog has a distinctive pattern of expression in the developing nervous system of the mouse, where it is found in postmitotic neurons from the first stages of neuronal differentiation (9.5 day postcoitus). The SEX protein (220 kD) is glycosylated and exposed at the cell surface. Maestrini et al. (1996) noted that, unlike the receptors of the HGF family, p220 (SEX), neither a MET-SEX chimera nor a constitutively dimerized TPR-SEX showed tyrosinase kinase activity. The data defined a gene family, called the SEX family by the authors, involved in the development of neural and epithelial tissues which encodes putative receptors with unexpected enzymatic and binding properties.
Tran et al. (2009) demonstrated that a secreted semaphorin, Sema3F (601124), is a negative regulator of spine development and synaptic structure. Mice with null mutations in genes encoding Sema3F, and its holoreceptor components neuropilin-2 (NPN2; 602070) and PlexA3, exhibit increased dentate gyrus granule cell and cortical layer V pyramidal neuron spine number and size, and also aberrant spine distribution. Moreover, Sema3F promotes loss of spines and excitatory synapses in dissociated neurons in vitro, and in Npn2-null brain slices cortical layer V and dentate gyrus granule cells exhibit increased miniature excitatory postsynaptic current frequency. In contrast, a distinct Sema3A (603961)-Npn1 (602069)/PlexA4 (604280) signaling cascade controls basal dendritic arborization in layer V cortical neurons, but does not influence spine morphogenesis or distribution. These disparate effects of secreted semaphorins are reflected in the restricted dendritic localization of Npn2 to apical dendrites and of Npn1 to all dendrites of cortical pyramidal neurons. Therefore, Sema3F signaling controls spine distribution along select dendritic processes, and distinct secreted semaphorin signaling events orchestrate central nervous system connectivity through the differential control of spine morphogenesis, synapse formation, and elaboration of dendritic morphology.
Maestrini et al. (1996) stated that the gene was named SEX 'since it maps on the long arm of the sex chromosome X.' They stated further that the 'three SEX-related sequences were named SEP, OCT, and NOV, according to the Latin ordinals following six.' Tamagnone et al. (1999) proposed a novel nomenclature for the genes of the plexin family, which they grouped into the A, B, C, and D subfamilies; the PLXN4 gene was renamed plexin A3 by them.
Maestrini, E., Tamagnone, L., Longati, P., Cremona, O., Gulisano, M., Bione, S., Tamanini, F., Neel, B. G., Toniolo, D., Comoglio, P. M. A family of transmembrane proteins with homology to the MET-hepatocyte growth factor receptor. Proc. Nat. Acad. Sci. 93: 674-678, 1996. [PubMed: 8570614] [Full Text: https://doi.org/10.1073/pnas.93.2.674]
Tamagnone, L., Artigiani, S., Chen, H., He, Z., Ming, G., Song, H., Chedotal, A., Winberg, M. L., Goodman, C. S., Poo, M., Tessier-Lavigne, M., Comoglio, P. M. Plexins are a large family of receptors for transmembrane, secreted, and GPI-anchored semaphorins in vertebrates. Cell 99: 71-80, 1999. Note: Erratum: Cell 104: following 320, 2001. [PubMed: 10520995] [Full Text: https://doi.org/10.1016/s0092-8674(00)80063-x]
Tran, T. S., Rubio, M. E., Clem, R. L., Johnson, D., Case, L., Tessier-Lavigne, M., Huganir, R. L., Ginty, D. D., Kolodkin, A. L. Secreted semaphorins control spine distribution and morphogenesis in the postnatal CNS. Nature 462: 1065-1069, 2009. [PubMed: 20010807] [Full Text: https://doi.org/10.1038/nature08628]