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Developmentally regulated GTP-binding protein 2 coordinates Rab5 activity and transferrin recycling

The small GTPase Rab5 regulates the early endocytic pathway of transferrin (Tfn), and Rab5 deactivation is required for Tfn recycling. Rab5 deactivation is achieved by RabGAP5, a GTPase-activating protein, on the endosomes. Here we report that recruitment of RabGAP5 is insufficient to deactivate Rab...

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Autores principales: Mani, Muralidharan, Lee, Unn Hwa, Yoon, Nal Ae, Kim, Hyo Jeong, Ko, Myoung Seok, Seol, Wongi, Joe, Yeonsoo, Chung, Hun Taeg, Lee, Byung Ju, Moon, Chang Hoon, Cho, Wha Ja, Park, Jeong Woo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4713135/
https://www.ncbi.nlm.nih.gov/pubmed/26582392
http://dx.doi.org/10.1091/mbc.E15-08-0558
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author Mani, Muralidharan
Lee, Unn Hwa
Yoon, Nal Ae
Kim, Hyo Jeong
Ko, Myoung Seok
Seol, Wongi
Joe, Yeonsoo
Chung, Hun Taeg
Lee, Byung Ju
Moon, Chang Hoon
Cho, Wha Ja
Park, Jeong Woo
author_facet Mani, Muralidharan
Lee, Unn Hwa
Yoon, Nal Ae
Kim, Hyo Jeong
Ko, Myoung Seok
Seol, Wongi
Joe, Yeonsoo
Chung, Hun Taeg
Lee, Byung Ju
Moon, Chang Hoon
Cho, Wha Ja
Park, Jeong Woo
author_sort Mani, Muralidharan
collection PubMed
description The small GTPase Rab5 regulates the early endocytic pathway of transferrin (Tfn), and Rab5 deactivation is required for Tfn recycling. Rab5 deactivation is achieved by RabGAP5, a GTPase-activating protein, on the endosomes. Here we report that recruitment of RabGAP5 is insufficient to deactivate Rab5 and that developmentally regulated GTP-binding protein 2 (DRG2) is required for Rab5 deactivation and Tfn recycling. DRG2 was associated with phosphatidylinositol 3-phosphate–containing endosomes. It colocalized and interacted with EEA1 and Rab5 on endosomes in a phosphatidylinositol 3-kinase–dependent manner. DRG2 depletion did not affect Tfn uptake and recruitment of RabGAP5 and Rac1 to Rab5 endosomes. However, it resulted in impairment of interaction between Rab5 and RabGAP5, Rab5 deactivation on endosomes, and Tfn recycling. Ectopic expression of shRNA-resistant DRG2 rescued Tfn recycling in DRG2-depleted cells. Our results demonstrate that DRG2 is an endosomal protein and a key regulator of Rab5 deactivation and Tfn recycling.
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spelling pubmed-47131352016-03-30 Developmentally regulated GTP-binding protein 2 coordinates Rab5 activity and transferrin recycling Mani, Muralidharan Lee, Unn Hwa Yoon, Nal Ae Kim, Hyo Jeong Ko, Myoung Seok Seol, Wongi Joe, Yeonsoo Chung, Hun Taeg Lee, Byung Ju Moon, Chang Hoon Cho, Wha Ja Park, Jeong Woo Mol Biol Cell Articles The small GTPase Rab5 regulates the early endocytic pathway of transferrin (Tfn), and Rab5 deactivation is required for Tfn recycling. Rab5 deactivation is achieved by RabGAP5, a GTPase-activating protein, on the endosomes. Here we report that recruitment of RabGAP5 is insufficient to deactivate Rab5 and that developmentally regulated GTP-binding protein 2 (DRG2) is required for Rab5 deactivation and Tfn recycling. DRG2 was associated with phosphatidylinositol 3-phosphate–containing endosomes. It colocalized and interacted with EEA1 and Rab5 on endosomes in a phosphatidylinositol 3-kinase–dependent manner. DRG2 depletion did not affect Tfn uptake and recruitment of RabGAP5 and Rac1 to Rab5 endosomes. However, it resulted in impairment of interaction between Rab5 and RabGAP5, Rab5 deactivation on endosomes, and Tfn recycling. Ectopic expression of shRNA-resistant DRG2 rescued Tfn recycling in DRG2-depleted cells. Our results demonstrate that DRG2 is an endosomal protein and a key regulator of Rab5 deactivation and Tfn recycling. The American Society for Cell Biology 2016-01-15 /pmc/articles/PMC4713135/ /pubmed/26582392 http://dx.doi.org/10.1091/mbc.E15-08-0558 Text en © 2016 Mani et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Mani, Muralidharan
Lee, Unn Hwa
Yoon, Nal Ae
Kim, Hyo Jeong
Ko, Myoung Seok
Seol, Wongi
Joe, Yeonsoo
Chung, Hun Taeg
Lee, Byung Ju
Moon, Chang Hoon
Cho, Wha Ja
Park, Jeong Woo
Developmentally regulated GTP-binding protein 2 coordinates Rab5 activity and transferrin recycling
title Developmentally regulated GTP-binding protein 2 coordinates Rab5 activity and transferrin recycling
title_full Developmentally regulated GTP-binding protein 2 coordinates Rab5 activity and transferrin recycling
title_fullStr Developmentally regulated GTP-binding protein 2 coordinates Rab5 activity and transferrin recycling
title_full_unstemmed Developmentally regulated GTP-binding protein 2 coordinates Rab5 activity and transferrin recycling
title_short Developmentally regulated GTP-binding protein 2 coordinates Rab5 activity and transferrin recycling
title_sort developmentally regulated gtp-binding protein 2 coordinates rab5 activity and transferrin recycling
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4713135/
https://www.ncbi.nlm.nih.gov/pubmed/26582392
http://dx.doi.org/10.1091/mbc.E15-08-0558
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