Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Mani M

PROVIDER: S-EPMC4713135 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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

Mani Muralidharan M Lee Unn Hwa UH Yoon Nal Ae NA Kim Hyo Jeong HJ Ko Myoung Seok MS Seol Wongi W Joe Yeonsoo Y Chung Hun Taeg HT Lee Byung Ju BJ Moon Chang Hoon CH Cho Wha Ja WJ Park Jeong Woo JW

Molecular biology of the cell 20151118 2

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. I ...[more]

PMID: 26582392

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Dataset Information

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

Publications

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

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