Experimental manipulation of phosphoinositide lipids: from cells to organisms. Issue 5 (May 2022)

• Record Type: Journal Article
• Authors: Doumane, Mehdi; Caillaud, Marie-Cécile; Jaillais, Yvon
• Is Part Of: Trends in cell biology. Volume 32:Issue 5(2022)
• Page Start: 445
• Page End: 461
• Publication Date: 2022-05
• Subjects: optogenetics -- lipid -- membrane -- targeted manipulation -- model organism; Cytology -- Periodicals; Cytology -- Research -- Periodicals; 571.6
• DOI: 10.1016/j.tcb.2022.01.009
• Languages: English
• ISSNs: 0962-8924

Abstract

Abstract : Phosphoinositides (PIs) have critical roles in various cellular, physiological, developmental, pathological, and infectious processes. They are signaling phospholipids that can affect every aspect of membrane biology, including protein function (e.g., recruitment and activity), membrane physicochemical properties (e.g., curvature, surface charges, and packing), and the generation of secondary messengers. PIs act at precise locations within the cell in a dose-dependent manner, and their local concentration can vary drastically during signaling and trafficking. Thus, techniques able to manipulate PI amounts acutely and with subcellular accuracy are paramount to understanding the role of these lipids in vivo . Here, we review these methods and emphasize approaches recently developed to perturb PI levels in multicellular organisms. Highlights: Phosphoinositides (PIs) are signaling lipids, either because they are precursors of secondary messengers or variations in their local quantity act as a signal in itself. PI metabolism is fast and interdependent because they are rapidly converted into each other by kinases and phosphatases. Mutations of PI enzymes impact development, but it is difficult to untangle the direct from indirect phenotypes induced by chronic PI perturbations. Experimental systems can acutely manipulate PI levels with subcellular accuracy in cultured cells. These include chemogenetic, voltogenetic, and optogenetic strategies, and operate in relevant time frames that are faster than endogenous PI metabolism. Systems for the inducible manipulation of PIs are becoming available in multicellular organisms, which enable researchers to address the function of these lipids during development and in their in vivo physiological context.