Calumenin-1 Interacts with Climp63 to Cooperatively Determine the Luminal Width and Distribution of Endoplasmic Reticulum Sheets.

Jianguo Chen,Birong Shen,Qingzhou Chen,Nannan Qian,Xin Zhou,Pengli Zheng,Junjie Hu,Junlin Teng

doi:10.1016/j.isci.2019.10.067

Abstract

SummaryThe ER is composed of distinct structures like tubules, matrices, and sheets, all of which are important for its various functions. However, how these distinct ER structures, especially the perinuclear ER sheets, are formed remains unclear. We report here that the ER membrane protein Climp63 and the ER luminal protein calumenin-1 (Calu1) collaboratively maintain ER sheet morphology. We show that the luminal length of Climp63 is positively correlated with the luminal width of ER sheets. Moreover, the lumen-only mutant of Climp63 dominant-negatively narrows the lumen of ER sheets, demonstrating that Climp63 acts as an ER luminal bridge. We also reveal that Calu1 specifically interacts with Climp63 and antagonizes Climp63 in terms of both ER sheet distribution and luminal width. Together, our data provide insight into how the structure of ER sheets is maintained and regulated.

Highlights

The ER is a continuous and highly dynamic membrane system distributing throughout the cytoplasm (Zhang and Hu, 2016)
Climp63 Determines the Luminal Width of ER Sheets Climp63 is composed of a 109-amino-acid cytoplasmic tail, a single transmembrane domain, and a large ER luminal segment
Knockout of Climp63 led to much narrower sheet lumen (30 nm compared with 50 nm in wild-type U2OS cells) (Figures 1C and 1D), which was consistent with the previous report (Shibata et al, 2010)

Summary

Introduction

The ER is a continuous and highly dynamic membrane system distributing throughout the cytoplasm (Zhang and Hu, 2016). ER in mammalian cells is composed of a nuclear envelope and a peripheral network, which includes different structures like tubules, sheets, and matrices (Nixon-Abell et al, 2016; Schroeder et al, 2018; Shibata et al, 2010). The ER sheets contain adherent ribosomes and are critical for luminal, membrane, and extracellular protein synthesis. The tubular ER is required for multiple processes including lipid synthesis (English and Voeltz, 2013; Jacquemyn et al, 2017) and signaling with other membranous organelles (Zhang and Hu, 2016; Zheng et al, 2018). How ER structures and networks, especially ER sheets, are formed and regulated remain unclear. It is unknown whether ER luminal proteins contribute to the regulation of ER morphology

Methods

Results

Discussion

Conclusion