Septins tune lipid kinase activity and PI(4,5)P turnover during G-protein-coupled PLC signalling in vivo.
Title | Septins tune lipid kinase activity and PI(4,5)P turnover during G-protein-coupled PLC signalling in vivo. |
Publication Type | Journal Article |
Year of Publication | 2022 |
Authors | Kumari A, Ghosh A, Kolay S, Raghu P |
Journal | Life Sci Alliance |
Volume | 5 |
Issue | 6 |
Date Published | 2022 Jun |
ISSN | 2575-1077 |
Abstract | Phosphatidylinositol 4,5-bisphosphate [PI(4,5)P] hydrolysis by phospholipase C (PLC) is a conserved mechanism of signalling. Given the low abundance of PI(4,5)P, its hydrolysis needs to be coupled to resynthesis to ensure continued PLC activity; however, the mechanism by which depletion is coupled to resynthesis remains unknown. PI(4,5)P synthesis is catalyzed by the phosphorylation of phosphatidylinositol 4 phosphate (PI4P) by phosphatidylinositol 4 phosphate 5 kinase (PIP5K). In photoreceptors, photon absorption is transduced into PLC activity and during this process, PI(4,5)P is resynthesized by a PIP5K. However, the mechanism by which PIP5K activity is coupled to PI(4,5)P hydrolysis is unknown. In this study, we identify a unique isoform dPIP5K, that is both necessary and sufficient to mediate PI(4,5)P synthesis during phototransduction. Depletion of PNUT, a non-redundant subunit of the septin family, enhances dPIP5K activity in vitro and PI(4,5)P resynthesis in vivo; co-depletion of dPIP5K reverses the enhanced rate of PI(4,5)P resynthesis in vivo. Thus, our work defines a septin-mediated mechanism through which PIP5K activity is coupled to PLC-mediated PI(4,5)P hydrolysis. |
DOI | 10.26508/lsa.202101293 |
Alternate Journal | Life Sci Alliance |
PubMed ID | 35277468 |