Cholesterol Regulates Syntaxin 6 Trafficking at trans-Golgi Network Endosomal Boundaries

被引：93

作者：

Reverter, Meritxell ^{[1
]}

Rentero, Carles ^{[1
]}

Garcia-Melero, Ana ^{[1
]}

Hoque, Monira ^{[2
]}

Vila de Muga, Sandra ^{[1
]}

Alvarez-Guaita, Anna ^{[1
]}

Conway, James R. W. ^{[3
,4
]}

Wood, Peta ^{[2
]}

Cairns, Rose ^{[2
]}

Lykopoulou, Lilia ^{[5
]}

Grinberg, Daniel ^{[6
]}

Vilageliu, Lluisa ^{[6
]}

Bosch, Marta ^{[7
]}

Heeren, Joerg ^{[8
]}

Blasi, Juan ^{[9
]}

Timpson, Paul ^{[3
,4
]}

Pol, Albert ^{[1
,7
,10
]}

Tebar, Francesc ^{[1
,7
]}

Murray, Rachael Z. ^{[11
]}

Grewal, Thomas ^{[2
]}

Enrich, Carlos ^{[1
,7
]}

机构：

[1] Univ Barcelona, Fac Med, Dept Biol Cellular Immunol & Neurociencies, Barcelona 08036, Spain

[2] Univ Sydney, Fac Pharm, Sydney, NSW 2006, Australia

[3] Univ New S Wales, Fac Med, St Vincents Clin Sch, Garvan Inst Med Res, Sydney, NSW 2010, Australia

[4] Univ New S Wales, Fac Med, St Vincents Clin Sch, Kinghorn Canc Ctr,Canc Res Program, Sydney, NSW 2010, Australia

[5] Univ Athens, Aghia Sofia Childrens Hosp, Dept Pediat 1, Athens 11527, Greece

[6] Univ Barcelona, Fac Biol, Dept Genet, CIBERER,IBUB, E-08028 Barcelona, Spain

[7] Inst Invest Biomed August Pi i Sunyer IDIBAPS, Ctr Recerca Biomed CELLEX, Barcelona 08036, Spain

[8] Univ Med Ctr Hamburg Eppendorf, Dept Biochem & Mol Biol Mol Cell Biol 2, D-20246 Hamburg, Germany

[9] Univ Barcelona, IDIBELL, Dept Pathol & Expt Therapeut, Barcelona 08907, Spain

[10] Inst Catalana Recerca & Estudis Avacats, Barcelona 08010, Spain

[11] Queensland Univ Technol, Inst Hlth & Biomed, Tissue Repair & Regenerat Program, Brisbane, Qld 4095, Australia

来源：

CELL REPORTS | 2014年 / 7卷 / 03期

基金：

澳大利亚国家健康与医学研究理事会; 英国医学研究理事会; 澳大利亚研究理事会;

关键词：

SNARE-MEDIATED TRAFFICKING; PICK C1 PROTEIN; CELL-MIGRATION; PLASMA-MEMBRANE; INTEGRIN; NPC1; ADHESION; COMPLEX; COMPARTMENTS; BINDING;

D O I：

10.1016/j.celrep.2014.03.043

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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 alpha Vb3 and alpha 5b1 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 proteinsmay play a regulatory role in cell migration and invasion.

引用

页码：883 / 897

页数：15

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