Unconventional protein secretion: membrane translocation of FGF-2 does not require protein unfolding
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Unconventional protein secretion: membrane translocation of FGF-2 does not require protein unfolding. / Backhaus, Rafael; Zehe, Christoph; Wegehingel, Sabine; Kehlenbach, Angelika; Schwappach, Blanche; Nickel, Walter.
in: J CELL SCI, Jahrgang 117, Nr. Pt 9, 01.04.2004, S. 1727-36.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Unconventional protein secretion: membrane translocation of FGF-2 does not require protein unfolding
AU - Backhaus, Rafael
AU - Zehe, Christoph
AU - Wegehingel, Sabine
AU - Kehlenbach, Angelika
AU - Schwappach, Blanche
AU - Nickel, Walter
PY - 2004/4/1
Y1 - 2004/4/1
N2 - 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.
AB - 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.
KW - Aminopterin/pharmacology
KW - Animals
KW - CHO Cells
KW - Cricetinae
KW - Fibroblast Growth Factor 2/chemistry
KW - Flow Cytometry
KW - Intracellular Membranes/metabolism
KW - Mice
KW - Microscopy, Confocal
KW - Mitochondria/metabolism
KW - Models, Biological
KW - Protein Conformation
KW - Protein Denaturation
KW - Protein Folding
KW - Protein Transport/drug effects
KW - Recombinant Fusion Proteins/chemistry
KW - Tetrahydrofolate Dehydrogenase/metabolism
KW - Transfection
U2 - 10.1242/jcs.01027
DO - 10.1242/jcs.01027
M3 - SCORING: Journal article
C2 - 15075234
VL - 117
SP - 1727
EP - 1736
JO - J CELL SCI
JF - J CELL SCI
SN - 0021-9533
IS - Pt 9
ER -
