Squaring the EMC – how promoting membrane protein biogenesis impacts cellular functions and organismal homeostasis

Norbert Volkmar,John C Christianson

doi:10.1242/jcs.243519

Abstract

ABSTRACTIntegral membrane proteins play key functional roles at organelles and the plasma membrane, necessitating their efficient and accurate biogenesis to ensure appropriate targeting and activity. The endoplasmic reticulum membrane protein complex (EMC) has recently emerged as an important eukaryotic complex for biogenesis of integral membrane proteins by promoting insertion and stability of atypical and sub-optimal transmembrane domains (TMDs). Although confirmed as a bona fide complex almost a decade ago, light is just now being shed on the mechanism and selectivity underlying the cellular responsibilities of the EMC. In this Review, we revisit the myriad of functions attributed the EMC through the lens of these new mechanistic insights, to address questions of the cellular and organismal roles the EMC has evolved to undertake.

Highlights

The eukaryotic endoplasmic reticulum (ER) houses the machinery responsible for biogenesis of secreted and integral membrane proteins
The ER membrane protein complex (EMC) has emerged as an important cog of the eukaryotic machinery handling membrane protein biogenesis, where it inserts suboptimal transmembrane domains (TMDs) and improves topological accuracy
Diverse phenotypic outcomes arising from its absence imply that EMC clients underlie a vast range of cellular processes

Summary

Introduction

The eukaryotic endoplasmic reticulum (ER) houses the machinery responsible for biogenesis of secreted and integral membrane proteins. The EMC has been implicated in polytopic membrane protein biogenesis (Louie et al, 2012; Richard et al, 2013; Satoh et al, 2015; Shurtleff et al, 2018; Chitwood et al, 2018; Coelho et al, 2019; Volkmar et al, 2019); a role potentially distinct from that of a TA insertase.

Results

Conclusion