SEC23-SEC31 the Interface Plays Critical Role for Export of Procollagen from the Endoplasmic Reticulum

Simeon A Boyadjiev,Kanika Bajaj Pahuja,Joonsik Yoon,Jinoh Kim,Lelio Orci,Susan Hammamoto,Randy Schekman,Sun-Don Kim,Mariella Ravazzola

doi:10.1074/jbc.m111.283382

Abstract

COPII proteins are essential for exporting most cargo molecules from the endoplasmic reticulum. The membrane-facing surface of the COPII proteins (especially SEC23-SEC24) interacts directly or indirectly with the cargo molecules destined for exit. As we characterized the SEC23A mutations at the SEC31 binding site identified from patients with cranio-lenticulo-sutural dysplasia, we discovered that the SEC23-SEC31 interface can also influence cargo selection. Remarkably, M702V SEC23A does not compromise COPII assembly, vesicle size, and packaging of cargo molecules into COPII vesicles that we have tested but induces accumulation of procollagen in the endoplasmic reticulum when expressed in normal fibroblasts. We observed that M702V SEC23A activates SAR1B GTPase more than wild-type SEC23A when SEC13-SEC31 is present, indicating that M702V SEC23A causes premature dissociation of COPII from the membrane. Our results indicate that a longer stay of COPII proteins on the membrane is required to cargo procollagen than other molecules and suggest that the SEC23-SEC31 interface plays a critical role in capturing various cargo molecules.

Highlights

SEC23 plays a critical role in generating transport vesicles from the endoplasmic reticulum (ER)
As we characterized the SEC23A mutations at the SEC31 binding site identified from patients with cranio-lenticulo-sutural dysplasia, we discovered that the SEC23-SEC31 interface can influence cargo selection
Our results indicate that a longer stay of COPII proteins on the membrane is required to cargo procollagen than other molecules and suggest that the SEC23-SEC31 interface plays a critical role in capturing various cargo molecules

Summary

Background

SEC23 plays a critical role in generating transport vesicles from the endoplasmic reticulum (ER). Results: SEC23A M702V mutation at the SEC23-SEC31 interface causes a selective retention of procollagen in the ER. Our results indicate that a longer stay of COPII proteins on the membrane is required to cargo procollagen than other molecules and suggest that the SEC23-SEC31 interface plays a critical role in capturing various cargo molecules. Similar cellular phenotypes have been observed in Caenorhabditis elegans sec mutants and in Danio rerio sec23a, or sec23b, or sec mutants These mutants fail to secrete extracellular matrix proteins, including collagen and possibly other cargo molecules needed for normal craniofacial and skeletal morphogenesis, leading to abnormal skeleton and cuticle (an exoskeleton) morphogenesis [5, 6, 8, 22]. Our study suggests that the SEC23-SEC31 interface is finely tailored for selecting variety of cargo molecules

EXPERIMENTAL PROCEDURES

RESULTS

DISCUSSION