Τίτλος:
Cholesterol Regulates Syntaxin 6 Trafficking at trans-Golgi Network Endosomal Boundaries
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Inhibition of cholesterol export from late endosomes causes cellular cholesterol imbalance, including cholesterol depletion in the trans-Golgi network (TGN). Here, using Chinese hamster ovary (CHO) Niemann-Pick type C1 (NPC1) mutant cell lines and human NPC1 mutant fibroblasts, we show that altered cholesterol levels at the TGN/endosome boundaries trigger Syntaxin 6 (Stx6) accumulation into VAMP3, transferrin, and Rab11-positive recycling endosomes (REs). This increases Stx6/VAMP3 interaction and interferes with the recycling of αVβ3 and α5β1 integrins and cell migration, possibly in a Stx6-dependent manner. In NPC1 mutant cells, restoration of cholesterol levels in the TGN, but not inhibition of VAMP3, restores the steady-state localization of Stx6 in the TGN. Furthermore, elevation of RE cholesterol is associated with increased amounts of Stx6 in RE. Hence, the fine-tuning of cholesterol levels at the TGN-RE boundaries together with a subset of cholesterol-sensitive SNARE proteins may play a regulatory role in cell migration and invasion. © 2014 The Authors.
Συγγραφείς:
Reverter, M.
Rentero, C.
Garcia-Melero, A.
Hoque, M.
Vilà de Muga, S.
Álvarez-Guaita, A.
Conway, J.R.W.
Wood, P.
Cairns, R.
Lykopoulou, L.
Grinberg, D.
Vilageliu, L.
Bosch, M.
Heeren, J.
Blasi, J.
Timpson, P.
Pol, A.
Tebar, F.
Murray, R.Z.
Grewal, T.
Enrich, C.
Περιοδικό:
Cell Reports Medicine
Λέξεις-κλειδιά:
cellubrevin; cholesterol; membrane protein; Rab11 protein; syntaxin; syntaxin 6; transferrin; unclassified drug; VAMP4 protein; very late activation antigen 5; vitronectin receptor; SNARE protein; carrier protein; cellubrevin; cholesterol; integrin alphavbeta1; membrane protein; NPC1 protein, human; protein binding; Rab protein; Rab11 protein; SNARE protein; syntaxin; very late activation antigen 5; vitronectin receptor, animal cell; article; cell migration; cellular distribution; CHO cell line; complex formation; controlled study; endosome; fibroblast; human; human cell; nonhuman; priority journal; protein protein interaction; trans Golgi network; Article; cell level; cell line; NPC1 cell line; protein expression; protein interaction; protein localization; protein transport; regulatory mechanism; signal transduction; animal; cell motion; chemistry; Cricetulus; endosome; genetics; hamster; metabolism; protein transport; trans Golgi network, Cricetulus griseus, Animals; Carrier Proteins; Cell Movement; CHO Cells; Cholesterol; Cricetinae; Cricetulus; Endosomes; Humans; Integrin alpha5beta1; Membrane Glycoproteins; Protein Binding; Protein Transport; Qa-SNARE Proteins; rab GTP-Binding Proteins; Receptors, Vitronectin; SNARE Proteins; trans-Golgi Network; Vesicle-Associated Membrane Protein 3
DOI:
10.1016/j.celrep.2014.03.043
