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VARP Is Recruited on to Endosomes by Direct Interaction with Retromer, Where Together They Function in Export to the Cell Surface
VARP is a Rab32/38 effector that also binds to the endosomal/lysosomal R-SNARE VAMP7. VARP binding regulates VAMP7 participation in SNARE complex formation and can therefore influence VAMP7-mediated membrane fusion events. Mutant versions of VARP that cannot bind Rab32:GTP, designed on the basis of...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4059916/ https://www.ncbi.nlm.nih.gov/pubmed/24856514 http://dx.doi.org/10.1016/j.devcel.2014.04.010 |
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author | Hesketh, Geoffrey G. Pérez-Dorado, Inmaculada Jackson, Lauren P. Wartosch, Lena Schäfer, Ingmar B. Gray, Sally R. McCoy, Airlie J. Zeldin, Oliver B. Garman, Elspeth F. Harbour, Michael E. Evans, Philip R. Seaman, Matthew N.J. Luzio, J. Paul Owen, David J. |
author_facet | Hesketh, Geoffrey G. Pérez-Dorado, Inmaculada Jackson, Lauren P. Wartosch, Lena Schäfer, Ingmar B. Gray, Sally R. McCoy, Airlie J. Zeldin, Oliver B. Garman, Elspeth F. Harbour, Michael E. Evans, Philip R. Seaman, Matthew N.J. Luzio, J. Paul Owen, David J. |
author_sort | Hesketh, Geoffrey G. |
collection | PubMed |
description | VARP is a Rab32/38 effector that also binds to the endosomal/lysosomal R-SNARE VAMP7. VARP binding regulates VAMP7 participation in SNARE complex formation and can therefore influence VAMP7-mediated membrane fusion events. Mutant versions of VARP that cannot bind Rab32:GTP, designed on the basis of the VARP ankyrin repeat/Rab32:GTP complex structure described here, unexpectedly retain endosomal localization, showing that VARP recruitment is not dependent on Rab32 binding. We show that recruitment of VARP to the endosomal membrane is mediated by its direct interaction with VPS29, a subunit of the retromer complex, which is involved in trafficking from endosomes to the TGN and the cell surface. Transport of GLUT1 from endosomes to the cell surface requires VARP, VPS29, and VAMP7 and depends on the direct interaction between VPS29 and VARP. Finally, we propose that endocytic cycling of VAMP7 depends on its interaction with VARP and, consequently, also on retromer. |
format | Online Article Text |
id | pubmed-4059916 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-40599162014-06-18 VARP Is Recruited on to Endosomes by Direct Interaction with Retromer, Where Together They Function in Export to the Cell Surface Hesketh, Geoffrey G. Pérez-Dorado, Inmaculada Jackson, Lauren P. Wartosch, Lena Schäfer, Ingmar B. Gray, Sally R. McCoy, Airlie J. Zeldin, Oliver B. Garman, Elspeth F. Harbour, Michael E. Evans, Philip R. Seaman, Matthew N.J. Luzio, J. Paul Owen, David J. Dev Cell Article VARP is a Rab32/38 effector that also binds to the endosomal/lysosomal R-SNARE VAMP7. VARP binding regulates VAMP7 participation in SNARE complex formation and can therefore influence VAMP7-mediated membrane fusion events. Mutant versions of VARP that cannot bind Rab32:GTP, designed on the basis of the VARP ankyrin repeat/Rab32:GTP complex structure described here, unexpectedly retain endosomal localization, showing that VARP recruitment is not dependent on Rab32 binding. We show that recruitment of VARP to the endosomal membrane is mediated by its direct interaction with VPS29, a subunit of the retromer complex, which is involved in trafficking from endosomes to the TGN and the cell surface. Transport of GLUT1 from endosomes to the cell surface requires VARP, VPS29, and VAMP7 and depends on the direct interaction between VPS29 and VARP. Finally, we propose that endocytic cycling of VAMP7 depends on its interaction with VARP and, consequently, also on retromer. Cell Press 2014-06-09 /pmc/articles/PMC4059916/ /pubmed/24856514 http://dx.doi.org/10.1016/j.devcel.2014.04.010 Text en © 2014 The Authors http://creativecommons.org/licenses/by/3.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/). |
spellingShingle | Article Hesketh, Geoffrey G. Pérez-Dorado, Inmaculada Jackson, Lauren P. Wartosch, Lena Schäfer, Ingmar B. Gray, Sally R. McCoy, Airlie J. Zeldin, Oliver B. Garman, Elspeth F. Harbour, Michael E. Evans, Philip R. Seaman, Matthew N.J. Luzio, J. Paul Owen, David J. VARP Is Recruited on to Endosomes by Direct Interaction with Retromer, Where Together They Function in Export to the Cell Surface |
title | VARP Is Recruited on to Endosomes by Direct Interaction with Retromer, Where Together They Function in Export to the Cell Surface |
title_full | VARP Is Recruited on to Endosomes by Direct Interaction with Retromer, Where Together They Function in Export to the Cell Surface |
title_fullStr | VARP Is Recruited on to Endosomes by Direct Interaction with Retromer, Where Together They Function in Export to the Cell Surface |
title_full_unstemmed | VARP Is Recruited on to Endosomes by Direct Interaction with Retromer, Where Together They Function in Export to the Cell Surface |
title_short | VARP Is Recruited on to Endosomes by Direct Interaction with Retromer, Where Together They Function in Export to the Cell Surface |
title_sort | varp is recruited on to endosomes by direct interaction with retromer, where together they function in export to the cell surface |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4059916/ https://www.ncbi.nlm.nih.gov/pubmed/24856514 http://dx.doi.org/10.1016/j.devcel.2014.04.010 |
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