A phosphatidylinositol phosphate kinase inhibits Ras activation and regulates chemorepulsion in Dictyostelium discoideum.

Autor:	Kirolos SA; Department of Biology, Texas A&M University, 301 Old Main Drive, College Station, TX 77843-3474, USA., Hatfield CE; Department of Biology, Texas A&M University, 301 Old Main Drive, College Station, TX 77843-3474, USA., Rahman RJ; Department of Biology, Texas A&M University, 301 Old Main Drive, College Station, TX 77843-3474, USA., Consalvo KM; Department of Biology, Texas A&M University, 301 Old Main Drive, College Station, TX 77843-3474, USA., Dittenhauser NK; Department of Biology, Texas A&M University, 301 Old Main Drive, College Station, TX 77843-3474, USA., Gomer RH; Department of Biology, Texas A&M University, 301 Old Main Drive, College Station, TX 77843-3474, USA.
Jazyk:	angličtina
Zdroj:	Journal of cell science [J Cell Sci] 2023 Jul 15; Vol. 136 (14). Date of Electronic Publication: 2023 Jul 27.
DOI:	10.1242/jcs.260541
Abstrakt:	During developmental and immune responses, cells move towards or away from some signals. Although much is known about chemoattraction, chemorepulsion (the movement of cells away from a stimulus) remains poorly understood. Proliferating Dictyostelium discoideum cells secrete a chemorepellent protein called AprA. Examining existing knockout strains, we previously identified proteins required for AprA-induced chemorepulsion, and a genetic screen suggested that the enzyme phosphatidylinositol phosphate kinase A (PIPkinA, also known as Pik6) might also be needed for chemorepulsion. Here, we show that cells lacking PIPkinA are not repelled by AprA, and that this phenotype is rescued by expression of PIPkinA. To bias cell movement, AprA inhibits Ras activation at the side of the cell closest to the source of AprA, and we find that PIPkinA is required for AprA to inhibit Ras activation. PIPkinA decreases levels of phosphatidylinositol 4-phosphate [PI(4)P] and phosphatidylinositol (3,4,5)-trisphosphate [PI(3,4,5)P3], and possibly because of these effects, potentiates phagocytosis and inhibits cell proliferation. Cells lacking PIPkinA show normal AprA binding, suggesting that PIPkinA regulates chemorepulsion at a step between the AprA receptor and AprA inhibition of Ras activation. Competing Interests: Competing interests The authors declare no competing or financial interests. (© 2023. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu