His domain protein tyrosine phosphatase and Rabaptin-5 couple endo-lysosomal sorting of EGFR with endosomal maturation.

ABSTRACT: His domain protein tyrosine phosphatase (HD-PTP; also known as PTPN23) collaborates with endosomal sorting complexes required for transport (ESCRTs) to sort endosomal cargo into intralumenal vesicles, forming the multivesicular body (MVB). Completion of MVB sorting is accompanied by maturation of the endosome into a late endosome, an event that requires inactivation of the early endosomal GTPase Rab5 (herein referring to generically to all isoforms). Here, we show that HD-PTP links ESCRT function with endosomal maturation. HD-PTP depletion prevents MVB sorting, while also blocking cargo from exiting Rab5-rich endosomes. HD-PTP-depleted cells contain hyperphosphorylated Rabaptin-5 (also known as RABEP1), a cofactor for the Rab5 guanine nucleotide exchange factor Rabex-5 (also known as RABGE

SUBMITTER: Parkinson G 

PROVIDER: S-EPMC8627557 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature