title: Sedlin controls the ER export of procollagen by regulating the Sar1 cycle.
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.
authors.affiliation: Telethon Institute of Genetics and Medicine, Naples, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Venditti
authors.forename: Tiziana
authors.initials: T
authors.lastname: Scanu
authors.forename: Michele
authors.initials: M
authors.lastname: Santoro
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Di Tullio
authors.forename: Alexander
authors.initials: A
authors.lastname: Spaar
authors.forename: Renato
authors.initials: R
authors.lastname: Gaibisso
authors.forename: Galina V
authors.initials: GV
authors.lastname: Beznoussenko
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Mironov
authors.forename: Alexander
authors.initials: A
authors.lastname: Mironov
authors.forename: Leopoldo
authors.initials: L
authors.lastname: Zelante
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Piemontese
authors.forename: Angelo
authors.initials: A
authors.lastname: Notarangelo
authors.forename: Vivek
authors.initials: V
authors.lastname: Malhotra
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Vertel
authors.forename: Cathal
authors.initials: C
authors.lastname: Wilson
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: De Matteis
mesh_terms: D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000378:metabolism*; D022181:COP-Coated Vesicles / Q000378:metabolism; D002460:Cell Line; D020219:Chondrogenesis / Q000235:genetics; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism*; D009154:Mutation; D010009:Osteochondrodysplasias / Q000235:genetics / Q000378:metabolism; D011347:Procollagen / Q000378:metabolism*; D021381:Protein Transport; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: C497396:ARNT protein, human; D026901:Membrane Transport Proteins; D011347:Procollagen; C120759:TRAPPC2 protein, human; D014157:Transcription Factors; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; C493083:SAR1A protein, human; D020559:Monomeric GTP-Binding Proteins