期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 105, 期 17, 页码 6308-6313出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0707601105
关键词
Alix; endocytosis; ESCRT
资金
- Biotechnology and Biological Sciences Research Council [BB/E019919/1] Funding Source: Medline
- Medical Research Council [G0001128, G0501725, G9722026] Funding Source: Medline
- BBSRC [BB/E019919/1] Funding Source: UKRI
- MRC [G9722026, G0501725, G0001128] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/E019919/1] Funding Source: researchfish
- Medical Research Council [G0501725, G9722026, G0001128] Funding Source: researchfish
The Saccharomyces cerevisiae protein Bro1p is required for sorting enclocytic cargo to the lumen of multivesicular bodies (MVBs). The mammalian ortholog of Bro1p is not known; although Alix, a structurally related protein, supports the topologically similar process of virus budding, functional studies have so far failed to identify a role for Alix in MVB formation. To establish whether Alix or similar protein(s) participate in endosomal sorting, we attached a retroviral peptide that binds Alix to a reporter receptor. This chimera was sorted efficiently away from the early endosome to the lumen of late enclocytic compartments. Surprisingly, sorting was not prevented by depleting Alix but instead required the Alix-related protein His domain phosphotyrosine phosphatase (HD-PTP)/His-Domain/Type N23 protein tyrosine phosphatase (PTPN23). Depletion of HD-PTP also reduced transfer of fluid-phase markers and EGF receptor to lysosomes, caused the accumulation of ubiquitinated proteins on endosomal compartments and disrupted the morphogenesis of MVBs. Rescue experiments using an RNAi-resistant version of HD-PTP and HD-PTP mutants demonstrated an essential role for the HD-PTP Bro1 domain, with ESCRT-III binding correlating with full biological activity.
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