Sandra Vilà de Muga
University of Barcelona
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Featured researches published by Sandra Vilà de Muga.
Traffic | 2007
Laia Cubells; Sandra Vilà de Muga; Francesc Tebar; Peta Wood; Rachael Evans; Mercedes Ingelmo-Torres; Maria Calvo; Katharina Gaus; Albert Pol; Thomas Grewal; Carlos Enrich
Annexin A6 (AnxA6) belongs to a family of Ca2+‐dependent membrane‐binding proteins and is involved in the regulation of endocytic and exocytic pathways. We previously demonstrated that AnxA6 regulates receptor‐mediated endocytosis and lysosomal targeting of low‐density lipoproteins and translocates to cholesterol‐enriched late endosomes (LE). As cholesterol modulates the membrane binding and the cellular location of AnxA6, but also affects the intracellular distribution of caveolin, we investigated the localization and trafficking of caveolin in AnxA6‐expressing cells. Here, we show that cells expressing high levels of AnxA6 are characterized by an accumulation of caveolin‐1 (cav‐1) in the Golgi complex. This is associated with a sequestration of cholesterol in the LE and lower levels of cholesterol in the Golgi and the plasma membrane, both likely contributing to retention of caveolin in the Golgi apparatus and a reduced number of caveolae at the cell surface. Further strengthening these findings, knock down of AnxA6 and the ectopic expression of the Niemann–Pick C1 protein in AnxA6‐overexpressing cells restore the cellular distribution of cav‐1 and cholesterol, respectively. In summary, this study demonstrates that elevated expression levels of AnxA6 perturb the intracellular distribution of cholesterol, which indirectly inhibits the exit of caveolin from the Golgi complex.
Cell Reports | 2014
Meritxell Reverter; Carles Rentero; Ana García-Melero; Monira Hoque; Sandra Vilà de Muga; Anna Alvarez-Guaita; James R.W. Conway; Peta Wood; Rose Cairns; Lilia Lykopoulou; Daniel Grinberg; Lluïsa Vilageliu; Marta Bosch; Joerg Heeren; Juan Blasi; Paul Timpson; Albert Pol; Francesc Tebar; Rachael Z. Murray; Thomas Grewal; Carlos Enrich
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.
Journal of Biological Chemistry | 2008
Laia Cubells; Sandra Vilà de Muga; Francesc Tebar; Joseph V. Bonventre; Jesús Balsinde; Albert Pol; Thomas Grewal; Carlos Enrich
The molecular mechanisms regulating the exit of caveolin from the Golgi complex are not fully understood. Cholesterol and sphingolipid availability affects Golgi vesiculation events and involves the activity of cytoplasmic phospholipase A2 (cPLA2). We recently demonstrated that high expression levels of annexin A6 (AnxA6) perturb the intracellular distribution of cellular cholesterol, thereby inhibiting caveolin export from the Golgi complex. In the present study we show that in Chinese hamster ovary cells overexpressing AnxA6, sequestration of cholesterol in late endosomes, leading to reduced amounts of cholesterol in the Golgi, inhibits cPLA2 activity and its association with the Golgi complex. This correlates with the blockage of caveolin export from the Golgi in cells treated with methyl arachidonyl fluorophosphonate, a Ca2+-dependent cPLA2 inhibitor. AnxA6-mediated down-regulation of cPLA2 activity was overcome upon the addition of exogenous cholesterol or transfection with small interfering RNA targeting AnxA6. These findings indicate that AnxA6 interferes with caveolin transport through the inhibition of cPLA2.
Biochimica et Biophysica Acta | 2011
Carlos Enrich; Carles Rentero; Sandra Vilà de Muga; Meritxell Reverter; Vishwaroop Mulay; Peta Wood; Meryem Koese; Thomas Grewal
Annexin A6 (AnxA6) belongs to a conserved family of Ca(2+)-dependent membrane-binding proteins. Like other annexins, the function of AnxA6 is linked to its ability to bind phospholipids in cellular membranes in a dynamic and reversible fashion, in particular during the regulation of endocytic and exocytic pathways. High amounts of AnxA6 sequester cholesterol in late endosomes, thereby lowering the levels of cholesterol in the Golgi and the plasma membrane. These AnxA6-dependent redistributions of cellular cholesterol pools give rise to reduced cytoplasmic phospholipase A2 (cPLA(2)) activity, retention of caveolin in the Golgi apparatus and a reduced number of caveolae at the cell surface. In addition to regulating cholesterol and caveolin distribution, AnxA6 acts as a scaffold/targeting protein for several signaling proteins, the best characterized being the Ca(2+)-dependent membrane targeting of p120GAP to downregulate Ras activity. AnxA6 also stimulates the Ca(2+)-inducible involvement of PKC in the regulation of HRas and possibly EGFR signal transduction pathways. The ability of AnxA6 to recruit regulators of the EGFR/Ras pathway is likely potentiated by AnxA6-induced actin remodeling. Accordingly, AnxA6 may function as an organizer of membrane domains (i) to modulate intracellular cholesterol homeostasis, (ii) to create a scaffold for the formation of multifactorial signaling complexes, and (iii) to regulate transient membrane-actin interactions during endocytic and exocytic transport. This article is part of a Special Issue entitled: 11th European Symposium on Calcium.
British Journal of Pharmacology | 2015
Anna Alvarez-Guaita; Sandra Vilà de Muga; Dylan M. Owen; David Williamson; Astrid Magenau; Ana García-Melero; Meritxell Reverter; Monira Hoque; Rose Cairns; Rhea Cornely; Francesc Tebar; Thomas Grewal; Katharina Gaus; Jesús Ayala-Sanmartín; Carlos Enrich; Carles Rentero
Annexin A6 (AnxA6) is a calcium‐dependent phospholipid‐binding protein that can be recruited to the plasma membrane to function as a scaffolding protein to regulate signal complex formation, endo‐ and exocytic pathways as well as distribution of cellular cholesterol. Here, we have investigated how AnxA6 influences the membrane order.
Molecular Biology of the Cell | 2011
Meritxell Reverter; Carles Rentero; Sandra Vilà de Muga; Anna Alvarez-Guaita; Vishwaroop Mulay; Rose Cairns; Peta Wood; Katia Monastyrskaya; Albert Pol; Francesc Tebar; J. Blasi; Thomas Grewal; Carlos Enrich
Molecular Biology of the Cell | 2008
Anna Lladó; Paul Timpson; Sandra Vilà de Muga; Jemina Moretó; Albert Pol; Thomas Grewal; Roger J. Daly; Carlos Enrich; Francesc Tebar
Cellular Signalling | 2006
Carles Rentero; Rachael Evans; Peta Wood; Francesc Tebar; Sandra Vilà de Muga; Laia Cubells; Iñaki de Diego; Toni E. Hayes; William E. Hughes; Albert Pol; Kerry-Anne Rye; Carlos Enrich; Thomas Grewal
Archive | 2014
Meritxell Reverter Martín; Carles Rentero Alfonso; Ana García-Melero; Monira Hoque; Sandra Vilà de Muga; Anna Alvarez-Guaita; James R.W. Conway; Peta Wood; Rose Cairns; Lila Lykopoulou; Daniel Raúl Grinberg Vaisman; Lluïsa Vilageliu i Arqués; Marta Bosch; Joerg Heeren; Joan Blasi Cabús; Paul Timpson; Albert Pol i Sorolla; Francesc Tebar Ramon; Rachael Z. Murray; Thomas Grewal
Faculty of Health; Institute of Health and Biomedical Innovation | 2014
Meritxell Reverter; Carles Rentero; Ana García-Melero; Monira Hoque; Sandra Vilà de Muga; Anna Alvarez-Guaita; James R.W. Conway; Peta Wood; Rose Cairns; Lilia Lykopoulou; Daniel Grinberg; Lluïsa Vilageliu; Marta Bosch; Joerg Heeren; Juan Blasi; Paul Timpson; Albert Pol; Francesc Tebar; Rachael Z. Murray; Thomas Grewal; Carlos Enrich