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Vps27 recruits ESCRT machinery to endosomes during MVB sorting
David J Katzmann1, Christopher J Stefan, Markus Babst
1Department of Cellular and Molecular Medicine, and Howard Hughes Medical Institute, University of California, San Diego School of Medicine, La Jolla, CA 92093-0688, USA.
The Journal of Cell Biology
|August 6, 2003
Summary
The multivesicular body (MVB) sorting pathway, crucial for protein degradation, relies on Vps27 and ESCRT-I interactions. Vps27 binds phosphatidylinositol 3-phosphate and ubiquitin, recruiting ESCRT-I to sort ubiquitinated proteins.
Area of Science:
- Cell Biology
- Molecular Biology
- Protein Degradation
Background:
- Lysosomal degradation of cell surface proteins requires the multivesicular body (MVB) sorting pathway.
- Class E vacuolar protein sorting (Vps) proteins, including ESCRT-I and Vps27 (Hrs), are essential for MVB pathway function.
- Vps27 and ESCRT-I interact with ubiquitin, a signal for MVB pathway entry.
Purpose of the Study:
- To elucidate the molecular mechanisms governing the activation and specificity of the MVB sorting pathway.
- To investigate the roles of Vps27, ESCRT-I, phosphatidylinositol 3-phosphate, and ubiquitin in MVB sorting.
Main Methods:
- Biochemical assays to study protein-protein and protein-lipid interactions.
- Analysis of Vps27 FYVE domain and COOH-terminal PTVP motif function.
- Investigating the recruitment of ESCRT-I to endosomal membranes.
Main Results:
- Vps27 activation of the MVB sorting reaction is mediated by interactions with phosphatidylinositol 3-phosphate via its FYVE domain.
- ESCRT-I binds to Vps27 on endosomal membranes through a COOH-terminal domain containing a PTVP motif.
- The PTVP motif in Vps27 is critical for MVB pathway function and ESCRT-I recruitment, showing homology to HIV-1 Gag.
Conclusions:
- Compartmental specificity of the MVB sorting pathway is achieved through Vps27 interactions with phosphatidylinositol 3-phosphate and ubiquitin.
- Vps27 acts as a scaffold, recruiting and activating ESCRT-I on endosomes to facilitate the sorting of ubiquitinated cargo.