In:
Molecular Biology of the Cell, American Society for Cell Biology (ASCB), Vol. 27, No. 2 ( 2016-01-15), p. 334-348
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.
Type of Medium:
Online Resource
ISSN:
1059-1524
,
1939-4586
DOI:
10.1091/mbc.e15-08-0558
Language:
English
Publisher:
American Society for Cell Biology (ASCB)
Publication Date:
2016
detail.hit.zdb_id:
1098979-1
detail.hit.zdb_id:
1474922-1
SSG:
12
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