Control of Rab7a activity and localization through endosomal type Igamma PIP 5-kinase is required for endosome maturation and lysosome function.

ABSTRACT: The small GTPase Ras-related protein Rab-7a (Rab7a) serves as a key organizer of the endosomal-lysosomal system. However, molecular mechanisms controlling Rab7a activation levels and subcellular translocation are still poorly defined. Here, we demonstrate that type Igamma phosphatidylinositol phosphate 5-kinase i5 (PIPKIγi5), an endosome-localized enzyme that produces phosphatidylinositol 4,5-bisphosphate, directly interacts with Rab7a and plays critical roles in the control of the endosomal-lysosomal system. The loss of PIPKIγi5 blocks Rab7a recruitment to early endosomes, which prevents the maturation of early to late endosomes. PIPKIγi5 loss disturbs retromer complex connection with Rab7a, which blocks the retrograde sorting of Cation-independent Mannose 6-Phosphate Receptor from late e

SUBMITTER: Sun M 

PROVIDER: S-EPMC7018547 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature