title: Concentration of Sec12 at ER exit sites via interaction with cTAGE5 is required for collagen export.
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.
authors.affiliation: 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.
authors.forename: Kota
authors.initials: K
authors.lastname: Saito
authors.affiliation: Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Koh
authors.initials: K
authors.lastname: Yamashiro
authors.affiliation: Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Shimazu
authors.affiliation: Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Tanabe
authors.affiliation: Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kontani
authors.affiliation: Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Katada
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000378:metabolism; D022181:COP-Coated Vesicles / Q000378:metabolism; D045744:Cell Line, Tumor; D024143:Collagen Type VII / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005260:Female; D006056:Golgi Apparatus; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D034622:RNA Interference; D034741:RNA, Small Interfering; D051381:Rats; D017208:Rats, Wistar; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000235:genetics
chemical_list: C497396:ARNT protein, human; D000951:Antigens, Neoplasm; D024143:Collagen Type VII; D004268:DNA-Binding Proteins; D020662:Guanine Nucleotide Exchange Factors; C109278:MIA2 protein, human; D009363:Neoplasm Proteins; C118971:PREB protein, human; D034741:RNA, Small Interfering; C517555:SEC16A protein, human; D014157:Transcription Factors; D033921:Vesicular Transport Proteins; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D006160:Guanosine Triphosphate; C493083:SAR1A protein, human; D020559:Monomeric GTP-Binding Proteins