Helmholtz Gemeinschaft


Roles of cholesterol and PtdIns(4,5)P(2) in the regulation of STIM1-Orai1 channel function

Item Type:Review
Title:Roles of cholesterol and PtdIns(4,5)P(2) in the regulation of STIM1-Orai1 channel function
Creators Name:Pacheco, J. and Bohórquez-Hernández, A. and Méndez-Acevedo, K.M. and Sampieri, A. and Vaca, L.
Abstract:Calcium is one of the most prominent second messengers. It is involved in a wide range of functions at the single-cell level but also in modulating regulatory mechanisms in the entire organism. One process mediating calcium signaling involves hydrolysis of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P(2)) by the phospholipase-C (PLC). Thus, calcium and PtdIns(4,5)P(2) are intimately intertwined two second-messenger cascades that often depend on each other. Another relevant lipid associated with calcium signaling is cholesterol. Both PtdIns(4,5)P(2) and cholesterol play key roles in the formation and maintenance of specialized signaling nanodomains known as lipid rafts. Lipid rafts are particularly important in calcium signaling by concentrating and localizing calcium channels such as the Orai1 channel. Depletion of internal calcium stores is initiated by the production of inositol-1,4,5-trisphosphate (IP3). Calcium depletion from the ER induces the oligomerization of STIM1, which binds Orai1 and initiates calcium influx into the cell. In the present review, we analyzed the complex interactions between cholesterol, PtdIns(4,5)P(2), and the complex formed by the Orai1 channel and the signaling molecule STIM1. We explore some of the complex mechanisms governing calcium homeostasis and phospholipid metabolism, as well as the interaction between these two apparently independent signaling cascades.
Keywords:SOCE, PtdIns(4,5)P(2), Cholesterol, STIM1, Orai1, ER-PM Junctions
Source:Advances in Experimental Medicine and Biology
Series Name:Advances in Experimental Medicine and Biology
Title of Book:Cholesterol and PI(4,5)P2 in vital biological functions : from coexistence to crosstalk
Page Range:305-326
Official Publication:https://doi.org/10.1007/978-3-031-21547-6_11
PubMed:View item in PubMed

Repository Staff Only: item control page

Open Access
MDC Library