Endoplasmic Reticulum-Plasma Membrane Contact Sites: Regulators, Mechanisms, and Physiological Functions.

Chenlu Li,Ruyue He,Chun Wan,Yinghui Liu,Tiantian Qian,Haijia Yu

doi:10.3389/fcell.2021.627700

Abstract

The endoplasmic reticulum (ER) forms direct membrane contact sites with the plasma membrane (PM) in eukaryotic cells. These ER-PM contact sites play essential roles in lipid homeostasis, ion dynamics, and cell signaling, which are carried out by protein-protein or protein-lipid interactions. Distinct tethering factors dynamically control the architecture of ER-PM junctions in response to intracellular signals or external stimuli. The physiological roles of ER-PM contact sites are dependent on a variety of regulators that individually or cooperatively perform functions in diverse cellular processes. This review focuses on proteins functioning at ER-PM contact sites and highlights the recent progress in their mechanisms and physiological roles.

Highlights

Intracellular trafficking between membrane-bound organelles is divided into two types, vesicular trafficking and non-vesicular trafficking
The mechanism and physiological function of stromal interaction molecule 1 (STIM1)-Orai1 needs a further study RASSF4 is a regulator of PI(4,5)P2 homeostasis that further regulates store-operated calcium entry (SOCE) transmembrane protein 110 (TMEM110) is a STIM-activating enhancer AC3 and AC8 interact with STIM1 and Orai1 separately to produce cAMP suppressor of actin 1 (Sac1) dephosphorylates PI(4)P to regulate phosphoinositide metabolism Protein tyrosine phosphatase 1B (PTP1B) dephosphorylates its substrates on the plasma membrane (PM), and plays roles in glucose metabolism, and other physiological processes ORPs located at endoplasmic reticulum (ER)-PM contact sites mediate the exchange of PI(4)P/PI(4,5)P2 with PS, their individual mechanism needs to be further studied
These key players cooperatively mediate the reactions between the opposed membranes and drive diverse fundamental cellular processes

Summary

Introduction

Intracellular trafficking between membrane-bound organelles is divided into two types, vesicular trafficking and non-vesicular trafficking. The ER forms extensive membrane junctions with the PM where LTPs play vital roles in the regulation of lipid metabolism as well as other physiological processes (Figures 4A,B) (Kentala et al, 2016; Saheki and De Camilli, 2017a; Cockcroft and Raghu, 2018; Jeyasimman and Saheki, 2019; Stefan, 2020).

Results

Conclusion