Concentration of Sec12 at ER exit sites via interaction with cTAGE5 is required for collagen export

Kota Saito; Koh Yamashiro; Noriko Shimazu; Tomoya Tanabe; Kenji Kontani; Toshiaki Katada

doi:10.1083/jcb.201312062

Concentration of Sec12 at ER exit sites via interaction with cTAGE5 is required for collagen export

J Cell Biol. 2014 Sep 15;206(6):751-62. doi: 10.1083/jcb.201312062. Epub 2014 Sep 8.

Authors

Kota Saito¹, Koh Yamashiro², Noriko Shimazu², Tomoya Tanabe², Kenji Kontani², Toshiaki Katada²

Affiliations

¹ Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan ksaito@mol.f.u-tokyo.ac.jp.
² Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.

Abstract

Mechanisms for exporting variably sized cargo from the endoplasmic reticulum (ER) using the same machinery remain poorly understood. COPII-coated vesicles, which transport secretory proteins from the ER to the Golgi apparatus, are typically 60-90 nm in diameter. However, collagen, which forms a trimeric structure that is too large to be accommodated by conventional transport vesicles, is also known to be secreted via a COPII-dependent process. In this paper, we show that Sec12, a guanine-nucleotide exchange factor for Sar1 guanosine triphosphatase, is concentrated at ER exit sites and that this concentration of Sec12 is specifically required for the secretion of collagen VII but not other proteins. Furthermore, Sec12 recruitment to ER exit sites is organized by its direct interaction with cTAGE5, a previously characterized collagen cargo receptor component, which functions together with TANGO1 at ER exit sites. These findings suggest that the export of large cargo requires high levels of guanosine triphosphate-bound Sar1 generated by Sec12 localized at ER exit sites.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antigens, Neoplasm / genetics
Antigens, Neoplasm / metabolism*
Aryl Hydrocarbon Receptor Nuclear Translocator / metabolism
COP-Coated Vesicles / metabolism
Cell Line, Tumor
Collagen Type VII / genetics
Collagen Type VII / metabolism*
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism*
Endoplasmic Reticulum / metabolism*
Female
Golgi Apparatus
Guanine Nucleotide Exchange Factors / genetics
Guanine Nucleotide Exchange Factors / metabolism*
Guanosine Triphosphate / metabolism
HEK293 Cells
HeLa Cells
Humans
Jurkat Cells
Monomeric GTP-Binding Proteins / metabolism*
Neoplasm Proteins / genetics
Neoplasm Proteins / metabolism*
Protein Transport
RNA Interference
RNA, Small Interfering
Rats
Rats, Wistar
Transcription Factors / genetics
Transcription Factors / metabolism*
Vesicular Transport Proteins / genetics

Substances

ARNT protein, human
Antigens, Neoplasm
Collagen Type VII
DNA-Binding Proteins
Guanine Nucleotide Exchange Factors
MIA2 protein, human
Neoplasm Proteins
PREB protein, human
RNA, Small Interfering
SEC16A protein, human
Transcription Factors
Vesicular Transport Proteins
Aryl Hydrocarbon Receptor Nuclear Translocator
Guanosine Triphosphate
SAR1A protein, human
Monomeric GTP-Binding Proteins