Alternative titles; symbols
HGNC Approved Gene Symbol: GOLGA4
Cytogenetic location: 3p22.2 Genomic coordinates (GRCh38): 3:37,243,271-37,366,879 (from NCBI)
To characterize the Golgi complex, Kooy et al. (1992) used serum from a Sjogren syndrome (270150) patient with a high titer of anti-Golgi autoantibodies. The serum immunoprecipitated a 230-kD protein that was specifically localized to the cytosolic surface of what was probably the trans-face of the Golgi stack. The 230-kD Golgi protein appeared to be a peripheral membrane component. The authors detected the 230-kD antigen in several cell types and species. By screening a HeLa cell cDNA expression library with the anti-Golgi autoantibodies, Erlich et al. (1996) identified a p230 cDNA. The 7.7-kb p230 mRNA encodes a 2,230-amino acid protein with a predicted coiled-coil structure, stabilized by heptad repeats. The p230 protein also contains a granin motif (see 113705). By SDS-PAGE, p230 from HeLa cells migrated as a 230-kD protein.
Independently, Fritzler et al. (1995) cloned a partial GOLGA4 cDNA, using serum from a Sjogren syndrome patient. Based on its predicted molecular mass, they designated the GOLGA4 protein golgin-245.
Using live-cell imaging, Lieu et al. (2008) showed that tubules and carriers expressing p230 selectively mediated TNF (191160) transport from the trans-Golgi network (TGN) in HeLa cells. Lipopolysaccharide (LPS) activation of macrophages caused a dramatic increase in p230-labeled tubules and carriers emerging from the TGN. Depletion of p230 in macrophages reduced cell surface delivery of TNF more than 10-fold compared with control cells. Mice with RNA interference-mediated silencing of p230 also had dramatically reduced surface expression of Tnf. Lieu et al. (2008) concluded that p230 is a key regulator of TNF secretion and that LPS activation of macrophages increases Golgi carriers for export.
Wong and Munro (2014) selected 10 mammalian golgins that are conserved outside of vertebrates and found on different regions of the Golgi and ectopically expressed them at the mitochondria through attachment to a mitochondrial transmembrane domain in place of their C-terminal Golgi targeting domain. The authors then used the distribution of cargo-laden vesicles originating from different locations as a readout for the golgins' tethering activity. Wong and Munro (2014) found that golgin-97 (GOLGA1; 602502), golgin-245 (GOLGA4), and GCC88 (607418) were able to capture endosome-to-Golgi cargoes; GM130 (GOLGA2; 602580) and GMAP210 (TRIP11; 604505) were able to capture endoplasmic reticulum (ER)-to-Golgi cargoes; and golgin-84 (GOLGA5; 606918), TMF1 (601126), and GMAP210 were able to capture Golgi resident proteins. Furthermore, electron microscopy yielded ultrastructural evidence for the accumulation of vesicular membranes around mitochondria decorated with specific golgins. Wong and Munro (2014) concluded that these data suggested that not only do the golgins capture vesicles, they also exhibit specificity toward vesicles of different origins: from the endosomes, from the ER, or from within the Golgi itself.
Daigo et al. (1999) determined that the GOLGA4 gene contains at least 11 exons.
By analysis of a cloned segment from chromosome 3p22-p21.3, Daigo et al. (1999) determined that the GOLGA4 gene is located in this region.
Daigo, Y., Isomura, M., Nishiwaki, T., Tamari, M., Ishikawa, S., Kai, M., Murata, Y., Takeuchi, K., Yamane, Y., Hayashi, R., Minami, M., Fujino, M. A., Hojo, Y., Uchiyama, I., Takagi, T., Nakamura, Y. Characterization of a 1200-kb genomic segment of chromosome 3p22-p21.3. DNA Res. 6: 37-44, 1999. [PubMed: 10231028] [Full Text: https://doi.org/10.1093/dnares/6.1.37]
Erlich, R., Gleeson, P. A., Campbell, P., Dietzsch, E., Toh, B.-H. Molecular characterization of trans-Golgi p230: a human peripheral membrane protein encoded by a gene on chromosome 6p12-22 contains extensive coiled-coil alpha-helical domains and a granin motif. J. Biol. Chem. 271: 8328-8337, 1996. [PubMed: 8626529] [Full Text: https://doi.org/10.1074/jbc.271.14.8328]
Fritzler, M. J., Lung, C.-C., Hamel, J. C., Griffith, K. J., Chan, E. K. L. Molecular characterization of golgin-245, a novel Golgi complex protein containing a granin signature. J. Biol. Chem. 270: 31262-31268, 1995. [PubMed: 8537393] [Full Text: https://doi.org/10.1074/jbc.270.52.31262]
Kooy, J., Toh, B.-H., Pettitt, J. M., Erlich, R., Gleeson, P. A. Human autoantibodies as reagents to conserved Golgi components: characterization of a peripheral, 230-kDa compartment-specific Golgi protein. J. Biol. Chem. 267: 20255-20263, 1992. [PubMed: 1400343]
Lieu, Z. Z., Lock, J. G., Hammond, L. A., La Gruta, N. L., Stow, J. L., Gleeson, P. A. A trans-Golgi network golgin is required for the regulated secretion of TNF in activated macrophages in vivo. Proc. Nat. Acad. Sci. 105: 3351-3356, 2008. [PubMed: 18308930] [Full Text: https://doi.org/10.1073/pnas.0800137105]
Wong, M., Munro, S. The specificity of vesicle traffic to the Golgi is encoded in the golgin coiled-coil proteins. Science 346: 1256898, 2014. Note: Electronic Article. [PubMed: 25359980] [Full Text: https://doi.org/10.1126/science.1256898]