Newly synthesized proteins exit the endoplasmic reticulum (ER) via coat protein complex II (COPII) vesicles. Procollagen (PC), however, forms prefibrils that are too large to fit into typical COPII vesicles; PC thus needs large transport carriers, which we term megacarriers. TANGO1 assists PC packing, but its role in promoting the growth of megacarriers is not known. We found that TANGO1 recruited Sedlin, a TRAPP component that is defective in spondyloepiphyseal dysplasia tarda (SEDT), and that Sedlin was required for the ER export of PC. Sedlin bound and promoted efficient cycling of Sar1, a guanosine triphosphatase that can constrict membranes, and thus allowed nascent carriers to grow and incorporate PC prefibrils. This joint action of TANGO1 and Sedlin sustained the ER export of PC, and its derangement may explain the defective chondrogenesis underlying SEDT.
Sedlin controls the ER export of procollagen by regulating the Sar1 cycle / Venditti, Rossella; Scanu, Tiziana; Santoro, Michele; Di Tullio, Giuseppe; Spaar, Alexander; Gaibisso, Renato; Beznoussenko, Galina V.; Mironov, Alexander A.; Alexander, Mironov J. r.; Zelante, Leopoldo; Piemontese, Maria Rosaria; Notarangelo, Angelo; Malhotra, Vivek; Vertel, Barbara M.; Wilson, Cathal; DE MATTEIS, Maria Antonietta. - In: SCIENCE. - ISSN 0036-8075. - 337:6102(2012), pp. 1668-1672. [10.1126/science.1224947]
Sedlin controls the ER export of procollagen by regulating the Sar1 cycle
Venditti, Rossella;DE MATTEIS, Maria Antonietta
2012
Abstract
Newly synthesized proteins exit the endoplasmic reticulum (ER) via coat protein complex II (COPII) vesicles. Procollagen (PC), however, forms prefibrils that are too large to fit into typical COPII vesicles; PC thus needs large transport carriers, which we term megacarriers. TANGO1 assists PC packing, but its role in promoting the growth of megacarriers is not known. We found that TANGO1 recruited Sedlin, a TRAPP component that is defective in spondyloepiphyseal dysplasia tarda (SEDT), and that Sedlin was required for the ER export of PC. Sedlin bound and promoted efficient cycling of Sar1, a guanosine triphosphatase that can constrict membranes, and thus allowed nascent carriers to grow and incorporate PC prefibrils. This joint action of TANGO1 and Sedlin sustained the ER export of PC, and its derangement may explain the defective chondrogenesis underlying SEDT.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
