A dPIP5K Dependent Pool of Phosphatidylinositol 4,5 Bisphosphate (PIP2) Is Required for G-Protein Coupled Signal Transduction in Drosophila Photoreceptors
| Autor: | Sourav Kolay, Amit Nair, Deepti Trivedi, Purbani Chakrabarti, Padinjat Raghu, Kamalesh Kumari, Shweta Yadav |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Phosphatidylinositol 4
5-Diphosphate Cancer Research Light Signal Transduction lcsh:QH426-470 G protein Biology Endocytosis Retina Cell membrane chemistry.chemical_compound Phosphoinositide Phospholipase C Phosphoinositide phospholipase C Genetics medicine Animals Photoreceptor Cells Molecular Biology Ocular Physiological Phenomena Genetics (clinical) Ecology Evolution Behavior and Systematics Cytoskeleton Cell Membrane Membrane Proteins Cell biology lcsh:Genetics Phosphotransferases (Alcohol Group Acceptor) medicine.anatomical_structure Drosophila melanogaster Phosphatidylinositol 4 5-bisphosphate chemistry Membrane protein lipids (amino acids peptides and proteins) Drosophila Signal transduction Visual phototransduction Research Article Signal Transduction |
| Zdroj: | PLoS Genetics PLoS Genetics, Vol 11, Iss 1, p e1004948 (2015) |
| ISSN: | 1553-7404 1553-7390 |
| Popis: | Multiple PIP2 dependent molecular processes including receptor activated phospholipase C activity occur at the neuronal plasma membranes, yet levels of this lipid at the plasma membrane are remarkably stable. Although the existence of unique pools of PIP2 supporting these events has been proposed, the mechanism by which they are generated is unclear. In Drosophila photoreceptors, the hydrolysis of PIP2 by G-protein coupled phospholipase C activity is essential for sensory transduction of photons. We identify dPIP5K as an enzyme essential for PIP2 re-synthesis in photoreceptors. Loss of dPIP5K causes profound defects in the electrical response to light and light-induced PIP2 dynamics at the photoreceptor membrane. Overexpression of dPIP5K was able to accelerate the rate of PIP2 synthesis following light induced PIP2 depletion. Other PIP2 dependent processes such as endocytosis and cytoskeletal function were unaffected in photoreceptors lacking dPIP5K function. These results provide evidence for the existence of a unique dPIP5K dependent pool of PIP2 required for normal Drosophila phototransduction. Our results define the existence of multiple pools of PIP2 in photoreceptors generated by distinct lipid kinases and supporting specific molecular processes at neuronal membranes. Author Summary PIP2 has been implicated in multiple functions at the plasma membrane. Some of these require its hydrolysis by receptor-activated phospholipase C, whereas others, such as membrane transport and cytoskeletal function, involve the interaction of the intact lipid with cellular proteins. The mechanistic basis underlying the segregation of these two classes of PIP2 dependent functions is unknown; it has been postulated that this might involve unique pools of PIP2 generated by distinct phosphoinsoitide kinases. We have studied this question in Drosophila photoreceptors, a model system where sensory transduction requires robust phospholipase C mediated PIP2 hydrolysis. We find that the activity of phosphatidylinositol-4-phosphate 5 kinase encoded by dPIP5K is required to support normal sensory transduction and PIP2 dynamics in photoreceptors. Remarkably, non-PLC dependent functions of PIP2, such as vesicular transport and the actin cytoskeleton, were unaffected in dPIP5K mutants. Thus, dPIP5K supports a pool of PIP2 that is readily available to PLC, but has no role in sustaining other non-PLC mediated PIP2 dependent processes. These findings support the existence of at least two non-overlapping pools of PIP2 at the plasma membrane, and provide a platform for future studies of PIP2 regulation at the plasma membrane. |
| Databáze: | OpenAIRE |
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