Cholesterol Regulates Syntaxin 6 Trafficking at trans-Golgi Network Endosomal Boundaries
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Cholesterol Regulates Syntaxin 6 Trafficking at trans-Golgi Network Endosomal Boundaries. / Reverter, Meritxell; Rentero, Carles; Garcia-Melero, Ana; Hoque, Monira; Vilà de Muga, Sandra; Alvarez-Guaita, Anna; Conway, James R W; Wood, Peta; Cairns, Rose; Lykopoulou, Lilia; Grinberg, Daniel; Vilageliu, Lluïsa; Bosch, Marta; Heeren, Joerg; Blasi, Juan; Timpson, Paul; Pol, Albert; Tebar, Francesc; Murray, Rachael Z; Grewal, Thomas; Enrich, Carlos.
In: CELL REP, Vol. 7, No. 3, 08.05.2014, p. 883-897.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Cholesterol Regulates Syntaxin 6 Trafficking at trans-Golgi Network Endosomal Boundaries
AU - Reverter, Meritxell
AU - Rentero, Carles
AU - Garcia-Melero, Ana
AU - Hoque, Monira
AU - Vilà de Muga, Sandra
AU - Alvarez-Guaita, Anna
AU - Conway, James R W
AU - Wood, Peta
AU - Cairns, Rose
AU - Lykopoulou, Lilia
AU - Grinberg, Daniel
AU - Vilageliu, Lluïsa
AU - Bosch, Marta
AU - Heeren, Joerg
AU - Blasi, Juan
AU - Timpson, Paul
AU - Pol, Albert
AU - Tebar, Francesc
AU - Murray, Rachael Z
AU - Grewal, Thomas
AU - Enrich, Carlos
N1 - Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.
PY - 2014/5/8
Y1 - 2014/5/8
N2 - 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.
AB - 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.
U2 - 10.1016/j.celrep.2014.03.043
DO - 10.1016/j.celrep.2014.03.043
M3 - SCORING: Journal article
C2 - 24746815
VL - 7
SP - 883
EP - 897
JO - CELL REP
JF - CELL REP
SN - 2211-1247
IS - 3
ER -