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|
|Date Published||2022 Jun|
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.
|Alternate Journal||Life Sci Alliance|