Cell Polarity, homeostasis
Our long-term scientific interest is to understand cellular communication mediated by lipid molecules generated by the metabolism of phosphatidylinositol. Phosphoinositide signals provide molecular control for key subcellular processes such as membrane remodelling, cytoskeletal function, transcription and translation. Through these processes, this signalling pathway orchestrates basic cellular behaviours such as cell division, shape changes, polarized movement and cell death and this plays a key role in a number of physiological processes including early embryogenesis, lymphocyte development and function as well as neuronal activity. The overall goal of our work is to understand how the architecture this signalling cascade is designed to optimally deliver physiological outputs. The work is multidisciplinary and done using a combination of Drosophila and human disease models. Over the last year we have uncovered the function of key enzymes that regulate lipid signaling and provided a molecular mechanism by which they control cellular processes. These include the mechanism by which lipid molecules are exchanged between cellular compartments, the control of membrane turnover and receptor activity by lipids and a quantitative model of the turnover of lipids during critical cell signaling reaction important for brain function. We also study the function of phosphoinositides in neuronal cell biology and brain disorders using human iPSC derived neural cells in cell culture. The goal of this work is to uncover the function of altered phosphoinositide signaling in brain disorders.
Panda A, Thakur R, Krishnan H, Naik A, Shinde D, Raghu P. Functional analysis of mammalian phospholipase D enzymes. Biosci Rep. 2018 Dec 7;38(6). pii:BSR20181690.
Balakrishnan SS, Basu U, Shinde D, Thakur R, Jaiswal M, Raghu P. Regulation of PI4P levels by PI4KIIIα during G-protein-coupled PLC signaling in Drosophila photoreceptors. J Cell Sci. 2018 Aug 3;131(15). pii: jcs217257.
Suratekar R, Panda A, Raghu P, Krishna S. Evidence of sinks and sources in the phospholipase C-activated PIP(2) cycle. FEBS Lett. 2018 Mar;592(6):962-972.
Ashe S, Malhotra V, Raghu P. Protein kinase D regulates metabolism and growth by controlling secretion of insulin like peptide. Dev Biol. 2018 Feb 1;434(1):175-185
Yadav S, Thakur R, Georgiev P, Deivasigamani S, Krishnan H, Ratnaparkhi G, Raghu P. RDGBα localization and function at membrane contact sites is regulated by FFAT-VAP interactions. J Cell Sci. 2018 Jan 8;131(1). pii: jcs207985.
Kamalesh K, Trivedi D, Toscano S, Sharma S, Kolay S, Raghu P. Phosphatidylinositol 5-phosphate 4-kinase regulates early endosomal dynamics during clathrin-mediated endocytosis. J Cell Sci. 2017 Jul 1;130(13):2119-2133
Thakur R, Panda A, Coessens E, Raj N, Yadav S, Balakrishnan S, Zhang Q, Georgiev P, Basak B, Pasricha R, Wakelam MJ, Ktistakis NT, Raghu P. Phospholipase D activity couples plasma membrane endocytosis with retromer dependent recycling. Elife. 2016 Nov 16;5. pii: e18515
Yadav S, Garner K, Georgiev P, Li M, Gomez-Espinosa E, Panda A, Mathre S, Okkenhaug H, Cockcroft S, Raghu P. RDGBα, a PtdIns-PtdOH transfer protein, regulates G-protein-coupled PtdIns(4,5)P2 signalling during Drosophila phototransduction. J Cell Sci. 2015 Sep 1;128(17):3330-44
Chakrabarti P, Kolay S, Yadav S, Kumari K, Nair A, Trivedi D, Raghu P. A dPIP5K dependent pool of phosphatidylinositol 4,5 bisphosphate (PIP2) is required for G-protein coupled signal transduction in Drosophila photoreceptors. PLoS Genet. 2015 Jan 29;11(1):e1004948
Cockcroft S, Raghu P. Phospholipid transport protein function at organelle contact sites. Curr Opin Cell Biol. 2018 Aug;53:52-60
Cockcroft S and Raghu P. Topological organisation of the phosphatidylinositol 4,5-bisphosphate-phospholipase C resynthesis cycle: PITPs bridge the ER–PM gap. Biochem J. 2016 Dec 1;473(23):4289-4310
Cockcroft S, Garner K, Yadav S, Gomez-Espinoza E, Raghu P. RdgBα reciprocally transfers PA and PI at ER-PM contact sites to maintain PI(4,5)P2 homoeostasis during phospholipase C signalling in Drosophila photoreceptors. Biochem Soc Trans. 2016 Feb;44(1):286-92
Yadav S, Cockcroft S and Raghu P. The Drosophila photoreceptor as a model system for studying signalling at membrane contact sites. Biochem Soc Trans. (2016) Apr 15;44(2):447-51.
Kolay, S., Basu, U and Raghu, P. Control of diverse sub-cellular processes by a single multi-functional lipid phosphatidylinositol 4,5 bisphosphate [PI(4,5)P2]. Biochemical Journal. (2016) Jun 15;473(12):1681-92.