Regulation of the COPII Secretory Machinery Via Focal Adhesions and Extracellular Matrix Signaling

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2022 Jul 13

PMID 35829701

Authors

Juan Jung

Muzamil Majid Khan

Jonathan Landry

Aliaksandr Halavatyi

Pedro Machado

Miriam Reiss

Rainer Pepperkok

Affiliations

Soon will be listed here.

Abstract

Proteins that enter the secretory pathway are transported from their place of synthesis in the endoplasmic reticulum to the Golgi complex by COPII-coated carriers. The networks of proteins that regulate these components in response to extracellular cues have remained largely elusive. Using high-throughput microscopy, we comprehensively screened 378 cytoskeleton-associated and related proteins for their functional interaction with the coat protein complex II (COPII) components SEC23A and SEC23B. Among these, we identified a group of proteins associated with focal adhesions (FERMT2, MACF1, MAPK8IP2, NGEF, PIK3CA, and ROCK1) that led to the downregulation of SEC23A when depleted by siRNA. Changes in focal adhesions induced by plating cells on ECM also led to the downregulation of SEC23A and decreases in VSVG transport from ER to Golgi. Both the expression of SEC23A and the transport defect could be rescued by treatment with a focal adhesion kinase inhibitor. Altogether, our results identify a network of cytoskeleton-associated proteins connecting focal adhesions and ECM-related signaling with the gene expression of the COPII secretory machinery and trafficking.

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