Alternative titles; symbols
HGNC Approved Gene Symbol: GPM6A
Cytogenetic location: 4q34.2 Genomic coordinates (GRCh38): 4:175,632,937-176,002,691 (from NCBI)
Yan et al. (1993) used monoclonal antibodies raised against antigens in mouse brain fractions to isolate 2 related cDNAs from an expression library. The cDNAs, which they designated M6a and M6b (300051), were highly similar to the myelin proteolipid protein (300401) and were expressed during early development of the mouse central nervous system (CNS). Olinsky et al. (1996) found that the M6a gene (GPM6A) was expressed only in neurons. They obtained partial human genomic and cDNA clones for M6a.
M6, a cell surface glycoprotein mainly expressed on neurons in the murine CNS, plays significant roles in neural cell adhesion and some aspects of neurite growth (Lagenaur et al., 1992). Shimizu et al. (1996) isolated a human cDNA that is highly homologous to the murine gene, symbolized Gpm6, that encodes M6. The human gene, GPM6A, contains an open reading frame of 834 nucleotides encoding a peptide of 278 amino acids. Northern blot analysis revealed specific expression in human brain.
Alfonso et al. (2005) stated that the M6a gene is downregulated in the hippocampus of both socially and physically stressed animals, and this effect is reversed by antidepressant treatment. By immunohistochemical analysis, they found that M6a was abundant in all rat hippocampal subregions, and it localized to membrane protrusions (filopodia/spines) of primary hippocampal neurons. M6a overexpression induced neurite formation and increased filopodia density in hippocampal neurons. Knockdown of M6a with small interfering RNA decreased filopodia number and reduced the density of synaptophysin (SYP; 313475) clusters. Alfonso et al. (2005) concluded that M6A has a role in neurite/filopodium outgrowth and synapse formation.
Olinsky et al. (1996) mapped the GPM6A gene to chromosome 4q34 by fluorescence in situ hybridization. By radiation hybrid mapping, Shimizu et al. (1996) assigned the GPM6A gene to chromosome 4q33-q34.
Alfonso, J., Fernandez, M. E., Cooper, B., Flugge, G., Frasch, A. C. The stress-regulated protein M6a is a key modulator for neurite outgrowth and filopodium/spine formation. Proc. Nat. Acad. Sci. 102: 17196-17201, 2005. [PubMed: 16286650] [Full Text: https://doi.org/10.1073/pnas.0504262102]
Lagenaur, C., Kunemund, V., Fischer, G., Fushiki, S., Schachner, M. Monoclonal M6 antibody interferes with neurite extension of cultured neurons. J. Neurobiol. 23: 71-88, 1992. [PubMed: 1564456] [Full Text: https://doi.org/10.1002/neu.480230108]
Olinsky, S., Loop, B. T., DeKosky, A., Ripepi, B., Weng, W., Cummins, J., Wenger, S. L., Yan, Y., Lagenaur, C., Narayanan, V. Chromosomal mapping of the human M6 genes. Genomics 33: 532-536, 1996. [PubMed: 8661015] [Full Text: https://doi.org/10.1006/geno.1996.0231]
Shimizu, F., Watanabe, T. K., Fujiwara, T., Takahashi, E., Nakamura, Y., Maekawa, H. Isolation and mapping of the human glycoprotein M6 gene (GPM6A) to 4q33-to-q34. Cytogenet. Cell Genet. 74: 138-139, 1996. [PubMed: 8893821] [Full Text: https://doi.org/10.1159/000134401]
Yan, Y., Lagenaur, C., Narayanan, V. Molecular cloning of M6: identification of a PLP/DM20 gene family. Neuron 11: 423-431, 1993. [PubMed: 8398137] [Full Text: https://doi.org/10.1016/0896-6273(93)90147-j]