Document Detail

Sedlin controls the ER export of procollagen by regulating the Sar1 cycle.
MedLine Citation:
PMID:  23019651     Owner:  NLM     Status:  MEDLINE    
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.
Rossella Venditti; Tiziana Scanu; Michele Santoro; Giuseppe Di Tullio; Alexander Spaar; Renato Gaibisso; Galina V Beznoussenko; Alexander A Mironov; Alexander Mironov; Leopoldo Zelante; Maria Rosaria Piemontese; Angelo Notarangelo; Vivek Malhotra; Barbara M Vertel; Cathal Wilson; Maria Antonietta De Matteis
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Science (New York, N.Y.)     Volume:  337     ISSN:  1095-9203     ISO Abbreviation:  Science     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-09-28     Completed Date:  2012-10-02     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  0404511     Medline TA:  Science     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1668-72     Citation Subset:  IM    
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MeSH Terms
Aryl Hydrocarbon Receptor Nuclear Translocator / metabolism*
COP-Coated Vesicles / metabolism
Cell Line
Chondrogenesis / genetics
Endoplasmic Reticulum / metabolism*
Golgi Apparatus / metabolism
Membrane Transport Proteins / genetics,  metabolism*
Monomeric GTP-Binding Proteins / metabolism*
Osteochondrodysplasias / genetics,  metabolism
Procollagen / metabolism*
Protein Transport
Transcription Factors / genetics,  metabolism*
Grant Support
AR053696/AR/NIAMS NIH HHS; GGP06166//Telethon; GGP07075//Telethon; GSP08002//Telethon; GTF08001//Telethon
Reg. No./Substance:
0/ARNT protein, human; 0/Membrane Transport Proteins; 0/Procollagen; 0/TRAPPC2 protein, human; 0/Transcription Factors; 138391-32-9/Aryl Hydrocarbon Receptor Nuclear Translocator; EC 3.6.1.-/SAR1A protein, human; EC GTP-Binding Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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