title: Dual function of cTAGE5 in collagen export from the endoplasmic reticulum.
abstract: Two independent functions of cTAGE5 have been reported in collagen VII export from the endoplasmic reticulum (ER). cTAGE5 not only forms a cargo receptor complex with TANGO1, but it also acts as a scaffold to recruit Sec12, a guanine-nucleotide exchange factor for Sar1 GTPase, to ER exit sites. However, the relationship between the two functions remains unclear. Here we isolated point mutants of cTAGE5 that lost Sec12-binding ability but retained binding to TANGO1. Although expression of the mutant alone could not rescue the defects in collagen VII secretion mediated by cTAGE5 knockdown, coexpression with Sar1, but not with the GTPase-deficient mutant, recovered secretion. The expression of Sar1 alone failed to rescue collagen secretion in cTAGE5-depleted cells. Taken together, these results suggest that two functionally irreplaceable and molecularly separable modules in cTAGE5 are both required for collagen VII export from the ER. The recruitment of Sec12 by cTAGE5 contributes to efficient activation of Sar1 in the vicinity of ER exit sites. In addition, the GTPase cycle of Sar1 appears to be responsible for collagen VII exit from the ER.
authors.affiliation: Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, 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, Tokyo 113-0033, Japan.
authors.forename: Miharu
authors.initials: M
authors.lastname: Maeda
authors.affiliation: Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, 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, Tokyo 113-0033, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Katada
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics* / Q000378:metabolism*; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000235:genetics / Q000378:metabolism; D022181:COP-Coated Vesicles / Q000378:metabolism; D018929:Cell Culture Techniques; D003094:Collagen / Q000378:metabolism; D024143:Collagen Type VII / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism*; D000069284:Protein Translocation Systems; D021381:Protein Transport; D014157:Transcription Factors / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000378:metabolism
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; D000069284:Protein Translocation Systems; D014157:Transcription Factors; D033921:Vesicular Transport Proteins; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D003094:Collagen; C493083:SAR1A protein, human; D020559:Monomeric GTP-Binding Proteins