title: TANGO1 facilitates cargo loading at endoplasmic reticulum exit sites.
abstract: A genome-wide screen revealed previously unidentified components required for transport and Golgi organization (TANGO). We now provide evidence that one of these proteins, TANGO1, is an integral membrane protein localized to endoplasmic reticulum (ER) exit sites, with a luminal SH3 domain and a cytoplasmic proline-rich domain (PRD). Knockdown of TANGO1 inhibits export of bulky collagen VII from the ER. The SH3 domain of TANGO1 binds to collagen VII; the PRD binds to the COPII coat subunits, Sec23/24. In this scenario, PRD binding to Sec23/24 subunits could stall COPII carrier biogenesis to permit the luminal domain of TANGO1 to guide SH3-bound cargo into a growing carrier. All cells except those of hematopoietic origin express TANGO1. We propose that TANGO1 exports other cargoes in cells that do not secrete collagen VII. However, TANGO1 does not enter the budding carrier, which represents a unique mechanism to load cargo into COPII carriers.
authors.affiliation: Department of Cell and Developmental Biology, CRG-Centre de Regulacio Genomica, Barcelona, Spain.
authors.forename: Kota
authors.initials: K
authors.lastname: Saito
authors.forename: Mei
authors.initials: M
authors.lastname: Chen
authors.forename: Fred
authors.initials: F
authors.lastname: Bard
authors.forename: Shenghong
authors.initials: S
authors.lastname: Chen
authors.forename: Huilin
authors.initials: H
authors.lastname: Zhou
authors.forename: David
authors.initials: D
authors.lastname: Woodley
authors.forename: Roman
authors.initials: R
authors.lastname: Polischuk
authors.forename: Randy
authors.initials: R
authors.lastname: Schekman
authors.forename: Vivek
authors.initials: V
authors.lastname: Malhotra
mesh_terms: D000818:Animals; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000378:metabolism*; D022181:COP-Coated Vesicles / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D004330:Drosophila / Q000166:cytology / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D021381:Protein Transport
chemical_list: D029721:Drosophila Proteins; C109766:tgo protein, Drosophila; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D003094:Collagen