TANGO1 Facilitates Cargo Loading at Endoplasmic Reticulum Exit Sites

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2008.12.025 Byline: Kota Saito (1), Mei Chen (3), Fred Bard (4), Shenghong Chen (5), Huilin Zhou (5), David Woodley (3), Roman Polischuk (6), Randy Schekman (7), Vivek Malhotra (1)(2) Keywords: CELLBIO; SIGNALING 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. Author Affiliation: (1) Department of Cell and Developmental Biology, CRG-Centre de Regulacio Genomica, Dr. Aiguader, 88 08003 Barcelona, Spain (2) Institutcio Catalana de Recerca I Estudis Avancats, Dr. Aiguader, 88 08003 Barcelona, Spain (3) Department of Dermatology, USC/Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, USA (4) Institute of Molecular and Cell Biology, 61 Biopolis Drive, 138673 Proteos, Singapore (5) Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA (6) Department of Cell Biology and Oncology, Consorzio Mario Negri Sud, 66030 Santa Maria Imbaro (Chieti), Italy (7) Department of Molecular and Cellular Biology, HHMI, University of California, Berkeley, Berkeley, CA 94720, USA Article History: Received 20 June 2008; Revised 8 October 2008; Accepted 12 December 2008 Article Note: (miscellaneous) Published: March 5, 2009