Alternative titles; symbols
HGNC Approved Gene Symbol: SNX9
Cytogenetic location: 6q25.3 Genomic coordinates (GRCh38): 6:157,823,246-157,945,077 (from NCBI)
Members of the sorting nexin protein family, such as SNX9, contain a phospholipid-binding module called the phox homology (PX) domain. SNX9 functions in clathrin (see 118955)-mediated endocytosis and clathrin-independent, actin (see 102610)-dependent fluid-phase endocytosis (Yarar et al., 2007).
By use of a yeast 2-hybrid screen, Howard et al. (1999) identified 2 SH3 domain-containing proteins, endophilin-1 (SH3GL2; 604465) and SNX9, that interact with the cytoplasmic domains of metalloprotease disintegrins ADAM9 (602713) and ADAM15 (605548). The 595-amino acid SNX9 protein contains an N-terminal SH3 domain, followed by a PX domain and a C-terminal coiled-coil domain. Northern blot analysis detected wide expression of 4.4- and 3.1-kb transcripts, with high levels in heart and placenta and relatively low levels in thymus and peripheral blood leukocytes.
Howard et al. (1999) determined that binding of the SH3 domain of SNX9 to ADAM9 and ADAM15 required the C-terminal proline-rich region of the ADAM9 and ADAM15 cytoplasmic tails. Both SNX9 and SH3GL2 preferentially bound the precursors, but not the processed forms, of ADAM9 and ADAM15.
Using green monkey kidney cells, Yarar et al. (2007) showed that SNX9 was required for clathrin-independent, actin-dependent fluid-phase endocytosis. SNX9 directly regulated F-actin nucleation through N-WASP (WASL; 605056) and the ARP2 (ACTR2; 604221)/ARP3 (ACTR3; 604222) complex, and this activity was synergistically enhanced by phosphatidylinositol(4,5)bisphosphate-containing liposomes. Yarar et al. (2007) concluded that SNX9 physically couples F-actin nucleation to plasma membrane remodeling during endocytosis.
Posor et al. (2013) showed that the BAR domain protein SNX9 is a phosphatidylinositol-3,4-bisphosphate (PI(3,4)P2) effector at clathrin-coated pits in clathrin-mediated endocytosis. Timed formation of PI(3,4)P2 by class 2 phosphatidylinositol-3-kinase C2A (PI3KC2A; 603601) is required for selective enrichment of SNX9 at late-stage endocytic intermediates.
Ma and Chircop (2012) found that human SNX9, SNX18, and SNX33 (619107) were required for efficient mitotic progression and completion. Depletion of SNX9, SNX18, or SNX33 caused cytokinesis failure in HeLa cells and resulted in multinucleation and delayed mitotic exit. SNX9, SNX18, and SNX33 had multiple points of action throughout mitosis and played different mitotic roles through cytokinesis. All 3 proteins were required for efficient endocytosis during interphase and cytokinesis, but not during metaphase, as endocytosis of transferrin (TF; 190000) was blocked by depletion of these proteins during interphase and cytokinesis. However, SNX9 had an additional role in ensuring efficient completion of chromosome alignment and segregation in early mitosis. Furthermore, all 3 proteins were required for localization of recycling endosomes to the cleavage furrow and the intracellular bridge (ICB) during cytokinesis. SNX9 played an additional role in accumulation of Golgi at the ICB during abscission.
Gross (2020) mapped the SNX9 gene to chromosome 6q25.3 based on an alignment of the SNX9 sequence (GenBank AF121859) with the genomic sequence (GRCh38).
Gross, M. B. Personal Communication. Baltimore, Md. 11/20/2020.
Howard, L., Nelson, K. K., Maciewicz, R. A., Blobel, C. P. Interaction of the metalloprotease disintegrins MDC9 and MDC15 with two SH3 domain-containing proteins, endophilin I and SH3PX1. J. Biol. Chem. 274: 31693-31699, 1999. [PubMed: 10531379] [Full Text: https://doi.org/10.1074/jbc.274.44.31693]
Ma, M. P. C., Chircop, M. SNX9, SNX18 and SNX33 are required for progression through and completion of mitosis. J. Cell Sci. 125: 4372-4382, 2012. [PubMed: 22718350] [Full Text: https://doi.org/10.1242/jcs.105981]
Posor, Y., Eichhorn-Gruenig, M., Puchkov, D., Schoneberg, J., Ullrich, A., Lampe, A., Muller, R., Zarbakhsh, S., Gulluni, F., Hirsch, E., Krauss, M., Schultz, C., Schmoranzer, J., Noe, F., Haucke, V. Spatiotemporal control of endocytosis by phosphatidylinositol-3,4-bisphosphate. Nature 499: 233-237, 2013. [PubMed: 23823722] [Full Text: https://doi.org/10.1038/nature12360]
Yarar, D., Waterman-Storer, C. M., Schmid, S. L. SNX9 couples actin assembly to phosphoinositide signals and is required for membrane remodeling during endocytosis. Dev. Cell 13: 43-56, 2007. [PubMed: 17609109] [Full Text: https://doi.org/10.1016/j.devcel.2007.04.014]