Alternative titles; symbols
HGNC Approved Gene Symbol: EXOC6
Cytogenetic location: 10q23.33 Genomic coordinates (GRCh38): 10:92,826,831-93,059,490 (from NCBI)
SEC15L1 is a subunit of the exocyst, a multisubunit complex first discovered for its requirement in the yeast secretory pathway (Wang et al., 2004).
Wang et al. (2004) noted that exocyst subunits have been found to associate with a subset of Golgi-derived vesicles and plasma membrane fractions in epithelial cell lines from several mammalian species. They found that several endogenous exocyst subunits, including Sec15, colocalized with microtubules and mitotic spindles in normal rat kidney cells. Wang et al. (2004) determined that mammalian exocyst complexes reconstituted from 8 recombinant subunits, including Sec15, inhibited tubulin polymerization in vitro. Deletion of Sec15 diminished the ability of the exocyst to inhibit tubulin polymerization.
The International Radiation Hybrid Mapping Consortium mapped the SEC15L1 gene to chromosome 10 (A006W20).
The mouse spontaneous mutation 'hemoglobin deficit' (hbd) impairs erythroid iron assimilation but does not cause other defects. Normal delivery of iron to developing erythroid precursors is highly dependent on the transferrin cycle. Through genetic mapping and complementation experiments, Lim et al. (2005) showed that the hbd mutation is an in-frame deletion of a conserved exon of the mouse gene Sec15l1, encoding 1 of 2 Sec15 proteins implicated in the mammalian exocyst complex. Sec15l1 is linked to the transferrin cycle through its interaction with Rab11 (see 605570), a GTPase involved in vesicular trafficking. Lim et al. (2005) proposed that inactivation of Sec15l1 alters recycling of transferrin cycle endosomes and increases the release of transferrin receptor exocytic vesicles. This in turn decreases erythroid iron uptake. Determining the molecular basis of the hbd phenotype provided new insight into the intricate mechanisms necessary for normal erythroid iron uptake and the function of a mammalian exocyst protein.
In lethal systemic anthrax, proliferating bacilli secrete large quantities of the toxins lethal factor (LF) and edema factor (EF), leading to widespread vascular leakage and shock. Host targets of LF (mitogen-activated protein-kinase kinases) and EF (cAMP-dependent processes) have been implicated in the initial phase of anthrax. In an investigation of toxin action during the final stage of infection, Guichard et al. (2010) used Drosophila melanogaster to identify the Rab11 (605570)/Sec15 exocyst, which acts at the last step of endocytic recycling, as a novel target of both EF and LF. EF reduces levels of apically localized Rab11 and indirectly blocks vesicle formation by its binding partner and effector Sec15 (Sec15-GFP), whereas LF acts more directly to reduce Sec15-GFP vesicles. Convergent effects of EF and LF on Rab11/Sec15 inhibited expression of and signaling by the Notch ligand Delta and reduced DE-cadherin levels at adherens junctions. In human endothelial cells, the 2 toxins acted in a conserved fashion to block formation of Sec15 vesicles, inhibit Notch signaling through Delta (DLL4; 605185), and reduce cadherin (CDH1; 192090) expression at adherens junctions. Guichard et al. (2010) suggested that this coordinated disruption of the Rab11/Sec15 exocyst by anthrax toxins may contribute to toxin-dependent barrier disruption and vascular dysfunction during Bacillus anthracis infection.
Guichard, A., McGillivray, S. M., Cruz-Moreno, B., van Sorge, N. M., Nizet, V., Bier, E. Anthrax toxins cooperatively inhibit endocytic recycling by the Rab11/Sec15 exocyst. Nature 467: 854-858, 2010. [PubMed: 20944747] [Full Text: https://doi.org/10.1038/nature09446]
Lim, J. E., Jin, O., Bennett, C., Morgan, K., Wang, F., Trenor, C. C., III, Fleming, M. D., Andrews, N. C. A mutation in Sec15l1 causes anemia in hemoglobin deficit (hbd) mice. Nature Genet. 37: 1270-1273, 2005. [PubMed: 16227995] [Full Text: https://doi.org/10.1038/ng1659]
Wang, S., Liu, Y., Adamson, C. L., Valdez, G., Guo, W., Hsu, S. C. The mammalian exocyst, a complex required for exocytosis, inhibits tubulin polymerization. J. Biol. Chem. 279: 35958-35966, 2004. [PubMed: 15205466] [Full Text: https://doi.org/10.1074/jbc.M313778200]