title: TFG Promotes Organization of Transitional ER and Efficient Collagen Secretion.
abstract: Collagen is the most abundant protein in the animal kingdom. It is of fundamental importance during development for cell differentiation and tissue morphogenesis as well as in pathological processes such as fibrosis and cancer cell migration. However, our understanding of the mechanisms of procollagen secretion remains limited. Here, we show that TFG organizes transitional ER (tER) and ER exit sites (ERESs) into larger structures. Depletion of TFG results in dispersion of tER elements that remain associated with individual ER-Golgi intermediate compartments (ERGICs) as largely functional ERESs. We show that TFG is not required for the transport and packaging of small soluble cargoes but is necessary for the export of procollagen from the ER. Our work therefore suggests a key relationship between the structure and function of ERESs and a central role for TFG in optimizing COPII assembly for procollagen export.
authors.affiliation: Cell Biology Laboratories, School of Biochemistry, Faculty of Biomedical Sciences, University of Bristol, University Walk, Bristol BS8 1TD, UK; Institut für Biophysik, Leibniz Universität Hannover, Herrenhäuserstraβe 2, 30419 Hannover, Germany.
authors.forename: Janine
authors.initials: J
authors.lastname: McCaughey
authors.affiliation: Cell Biology Laboratories, School of Biochemistry, Faculty of Biomedical Sciences, University of Bristol, University Walk, Bristol BS8 1TD, UK.
authors.forename: Victoria J
authors.initials: VJ
authors.lastname: Miller
authors.affiliation: Cell Biology Laboratories, School of Biochemistry, Faculty of Biomedical Sciences, University of Bristol, University Walk, Bristol BS8 1TD, UK.
authors.forename: Nicola L
authors.initials: NL
authors.lastname: Stevenson
authors.affiliation: Cell Biology Laboratories, School of Biochemistry, Faculty of Biomedical Sciences, University of Bristol, University Walk, Bristol BS8 1TD, UK.
authors.forename: Anna K
authors.initials: AK
authors.lastname: Brown
authors.affiliation: Cell Biology Laboratories, School of Biochemistry, Faculty of Biomedical Sciences, University of Bristol, University Walk, Bristol BS8 1TD, UK.
authors.forename: Annika
authors.initials: A
authors.lastname: Budnik
authors.affiliation: Proteomics Facility, Faculty of Biomedical Sciences, University of Bristol, University Walk, Bristol BS8 1TD, UK.
authors.forename: Kate J
authors.initials: KJ
authors.lastname: Heesom
authors.affiliation: Wolfson Bioimaging Facility, Faculty of Biomedical Sciences, University of Bristol, University Walk, Bristol BS8 1TD, UK.
authors.forename: Dominic
authors.initials: D
authors.lastname: Alibhai
authors.affiliation: Cell Biology Laboratories, School of Biochemistry, Faculty of Biomedical Sciences, University of Bristol, University Walk, Bristol BS8 1TD, UK. Electronic address: david.stephens@bristol.ac.uk.
authors.forename: David J
authors.initials: DJ
authors.lastname: Stephens
mesh_terms: D003094:Collagen / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D008361:Mannosidases / Q000378:metabolism; D008954:Models, Biological; D021381:Protein Transport; D011506:Proteins / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D015203:Reproducibility of Results; D033921:Vesicular Transport Proteins
chemical_list: D003094:Collagen; D049452:Green Fluorescent Proteins; D008361:Mannosidases; D011506:Proteins; D034741:RNA, Small Interfering; C096163:TFG protein, human; D033921:Vesicular Transport Proteins; C038829:mannosyl-oligosaccharide 1,3 - 1,6-alpha-mannosidase