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The Rab5 Effector Rabankyrin-5 Regulates and Coordinates Different Endocytic Mechanisms
The small GTPase Rab5 is a key regulator of clathrin-mediated endocytosis. On early endosomes, within a spatially restricted domain enriched in phosphatydilinositol-3-phosphate [PI(3)P], Rab5 coordinates a complex network of effectors that functionally cooperate in membrane tethering, fusion, and or...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2004
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC514490/ https://www.ncbi.nlm.nih.gov/pubmed/15328530 http://dx.doi.org/10.1371/journal.pbio.0020261 |
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author | Schnatwinkel, Carsten Christoforidis, Savvas Lindsay, Margaret R Uttenweiler-Joseph, Sandrine Wilm, Matthias Parton, Robert G Zerial, Marino |
author_facet | Schnatwinkel, Carsten Christoforidis, Savvas Lindsay, Margaret R Uttenweiler-Joseph, Sandrine Wilm, Matthias Parton, Robert G Zerial, Marino |
author_sort | Schnatwinkel, Carsten |
collection | PubMed |
description | The small GTPase Rab5 is a key regulator of clathrin-mediated endocytosis. On early endosomes, within a spatially restricted domain enriched in phosphatydilinositol-3-phosphate [PI(3)P], Rab5 coordinates a complex network of effectors that functionally cooperate in membrane tethering, fusion, and organelle motility. Here we discovered a novel PI(3)P-binding Rab5 effector, Rabankyrin-5, which localises to early endosomes and stimulates their fusion activity. In addition to early endosomes, however, Rabankyrin-5 localises to large vacuolar structures that correspond to macropinosomes in epithelial cells and fibroblasts. Overexpression of Rabankyrin-5 increases the number of macropinosomes and stimulates fluid-phase uptake, whereas its downregulation inhibits these processes. In polarised epithelial cells, this function is primarily restricted to the apical membrane. Rabankyrin-5 localises to large pinocytic structures underneath the apical surface of kidney proximal tubule cells, and its overexpression in polarised Madin-Darby canine kidney cells stimulates apical but not basolateral, non-clathrin-mediated pinocytosis. In demonstrating a regulatory role in endosome fusion and (macro)pinocytosis, our studies suggest that Rab5 regulates and coordinates different endocytic mechanisms through its effector Rabankyrin-5. Furthermore, its active role in apical pinocytosis in epithelial cells suggests an important function of Rabankyrin-5 in the physiology of polarised cells. |
format | Text |
id | pubmed-514490 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2004 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-5144902004-08-24 The Rab5 Effector Rabankyrin-5 Regulates and Coordinates Different Endocytic Mechanisms Schnatwinkel, Carsten Christoforidis, Savvas Lindsay, Margaret R Uttenweiler-Joseph, Sandrine Wilm, Matthias Parton, Robert G Zerial, Marino PLoS Biol Research Article The small GTPase Rab5 is a key regulator of clathrin-mediated endocytosis. On early endosomes, within a spatially restricted domain enriched in phosphatydilinositol-3-phosphate [PI(3)P], Rab5 coordinates a complex network of effectors that functionally cooperate in membrane tethering, fusion, and organelle motility. Here we discovered a novel PI(3)P-binding Rab5 effector, Rabankyrin-5, which localises to early endosomes and stimulates their fusion activity. In addition to early endosomes, however, Rabankyrin-5 localises to large vacuolar structures that correspond to macropinosomes in epithelial cells and fibroblasts. Overexpression of Rabankyrin-5 increases the number of macropinosomes and stimulates fluid-phase uptake, whereas its downregulation inhibits these processes. In polarised epithelial cells, this function is primarily restricted to the apical membrane. Rabankyrin-5 localises to large pinocytic structures underneath the apical surface of kidney proximal tubule cells, and its overexpression in polarised Madin-Darby canine kidney cells stimulates apical but not basolateral, non-clathrin-mediated pinocytosis. In demonstrating a regulatory role in endosome fusion and (macro)pinocytosis, our studies suggest that Rab5 regulates and coordinates different endocytic mechanisms through its effector Rabankyrin-5. Furthermore, its active role in apical pinocytosis in epithelial cells suggests an important function of Rabankyrin-5 in the physiology of polarised cells. Public Library of Science 2004-09 2004-08-24 /pmc/articles/PMC514490/ /pubmed/15328530 http://dx.doi.org/10.1371/journal.pbio.0020261 Text en Copyright: © Schnatwinkel 2004 et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Schnatwinkel, Carsten Christoforidis, Savvas Lindsay, Margaret R Uttenweiler-Joseph, Sandrine Wilm, Matthias Parton, Robert G Zerial, Marino The Rab5 Effector Rabankyrin-5 Regulates and Coordinates Different Endocytic Mechanisms |
title | The Rab5 Effector Rabankyrin-5 Regulates and Coordinates Different Endocytic Mechanisms |
title_full | The Rab5 Effector Rabankyrin-5 Regulates and Coordinates Different Endocytic Mechanisms |
title_fullStr | The Rab5 Effector Rabankyrin-5 Regulates and Coordinates Different Endocytic Mechanisms |
title_full_unstemmed | The Rab5 Effector Rabankyrin-5 Regulates and Coordinates Different Endocytic Mechanisms |
title_short | The Rab5 Effector Rabankyrin-5 Regulates and Coordinates Different Endocytic Mechanisms |
title_sort | rab5 effector rabankyrin-5 regulates and coordinates different endocytic mechanisms |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC514490/ https://www.ncbi.nlm.nih.gov/pubmed/15328530 http://dx.doi.org/10.1371/journal.pbio.0020261 |
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