title: Unconventional protein secretion: membrane translocation of FGF-2 does not require protein unfolding.
abstract: Endoplasmic reticulum/Golgi-dependent protein secretion depends on signal peptides that mediate membrane translocation of nascent secretory proteins into the lumen of the endoplasmic reticulum. Classical secretory proteins are transported across the membrane of the endoplasmic reticulum in an unfolded conformation, which is similar to protein import into mitochondria. This process is mediated by Sec61, the protein-conducting channel of the endoplasmic reticulum. Employing both FACS-based in vivo transport assays and confocal microscopy, we now show that fibroblast growth factor 2 (FGF-2), a pro-angiogenic mediator exported from mammalian cells by an unconventional secretory pathway, does not need to be unfolded in order to be released into the extracellular space. These findings suggest that the molecular apparatus mediating export of FGF-2 is not only distinct from classical translocation machineries in terms of molecular identity but also operates in a mechanistically distinct manner that allows membrane translocation of FGF-2 in a folded conformation.
authors.affiliation: Heidelberg University Biochemistry Center, Im Neuenheimer Feld 328, 69120 Heidelberg, Germany.
authors.forename: Rafael
authors.initials: R
authors.lastname: Backhaus
authors.forename: Christoph
authors.initials: C
authors.lastname: Zehe
authors.forename: Sabine
authors.initials: S
authors.lastname: Wegehingel
authors.forename: Angelika
authors.initials: A
authors.lastname: Kehlenbach
authors.forename: Blanche
authors.initials: B
authors.lastname: Schwappach
authors.forename: Walter
authors.initials: W
authors.lastname: Nickel
mesh_terms: D000630:Aminopterin / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D016222:Fibroblast Growth Factor 2 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D005434:Flow Cytometry; D007425:Intracellular Membranes / Q000378:metabolism*; D051379:Mice; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D011487:Protein Conformation; D011489:Protein Denaturation; D017510:Protein Folding; D021381:Protein Transport / Q000187:drug effects; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D013762:Tetrahydrofolate Dehydrogenase / Q000378:metabolism; D014162:Transfection
chemical_list: D011993:Recombinant Fusion Proteins; D016222:Fibroblast Growth Factor 2; D013762:Tetrahydrofolate Dehydrogenase; D000630:Aminopterin