Publication Date:
2012-09-29
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3471527/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3471527/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Venditti, Rossella -- Scanu, Tiziana -- Santoro, Michele -- Di Tullio, Giuseppe -- Spaar, Alexander -- Gaibisso, Renato -- Beznoussenko, Galina V -- Mironov, Alexander A -- Mironov, Alexander Jr -- Zelante, Leopoldo -- Piemontese, Maria Rosaria -- Notarangelo, Angelo -- Malhotra, Vivek -- Vertel, Barbara M -- Wilson, Cathal -- De Matteis, Maria Antonietta -- AR053696/AR/NIAMS NIH HHS/ -- GGP06166/Telethon/Italy -- GGP07075/Telethon/Italy -- GSP08002/Telethon/Italy -- GTF08001/Telethon/Italy -- New York, N.Y. -- Science. 2012 Sep 28;337(6102):1668-72.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Telethon Institute of Genetics and Medicine, Naples, Italy.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23019651" target="_blank"〉PubMed〈/a〉
Keywords:
Aryl Hydrocarbon Receptor Nuclear Translocator/*metabolism
;
COP-Coated Vesicles/metabolism
;
Cell Line
;
Chondrogenesis/genetics
;
Endoplasmic Reticulum/*metabolism
;
Golgi Apparatus/metabolism
;
Humans
;
Membrane Transport Proteins/genetics/*metabolism
;
Monomeric GTP-Binding Proteins/*metabolism
;
Mutation
;
Osteochondrodysplasias/genetics/metabolism
;
Procollagen/*metabolism
;
Protein Transport
;
Transcription Factors/genetics/*metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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