The Hsp90 chaperone complex regulates GDI-dependent Rab recycling
Christine Y Chen1, William E Balch
1Departments of *Cell Biology and Molecular Biology and The Institute for Childhood and Neglected Disease, The Scripps Research Institute, La Jolla, CA 92037.
Molecular Biology of the Cell
|May 12, 2006
Summary
The heat-shock protein 90 (Hsp90) chaperone system regulates Rab GTPase recycling, crucial for exocytic and endocytic pathways. Hsp90, with guanine nucleotide dissociation inhibitor (GDI), facilitates Rab1 recycling for ER-to-Golgi transport and Golgi assembly.
Area of Science:
- Cellular Biology
- Molecular Biology
- Biochemistry
Background:
- Rab GTPases are key regulators of membrane trafficking in eukaryotic cells.
- The membrome network integrates Rab GTPase activity to control exocytic and endocytic pathways.
- Understanding Rab GTPase recycling is essential for deciphering cellular transport dynamics.
Purpose of the Study:
- To investigate the role of the heat-shock protein 90 (Hsp90) chaperone system in Rab GTPase recycling.
- To elucidate the mechanism by which Hsp90 influences early exocytic pathways, specifically ER-to-Golgi transport.
- To determine if Hsp90's role in Rab recycling extends beyond ER-to-Golgi transport.
Main Methods:
- Investigated Hsp90-Guanine nucleotide dissociation inhibitor (GDI) complex formation.
- Utilized Hsp90-specific inhibitors (geldanamycin, 17-DMAG, radicicol) to assess ER-to-Golgi transport.
- Examined the effect of Hsp90 on Rab1 membrane retrieval and Golgi assembly.
- Compared Hsp90's role in Rab1 (ER-to-Golgi) and Rab3A (synaptic vesicle fusion) recycling.
Main Results:
- Hsp90 forms a complex with GDI to facilitate the recycling of Rab1, a client substrate essential for ER-to-Golgi transport.
- Inhibition of Hsp90 by geldanamycin, 17-DMAG, or radicicol blocks ER-to-Golgi traffic.
- Hsp90 activity is necessary for the formation of a functional GDI complex, enabling Rab1 membrane retrieval.
- Hsp90 is critical for Rab1-dependent Golgi assembly.
- Rab3A, involved in synaptic vesicle fusion, also requires Hsp90 for membrane retrieval.
Conclusions:
- The Hsp90 chaperone system is integral to Rab1 recycling in early exocytic pathways.
- Hsp90 plays a vital role in regulating ER-to-Golgi transport and Golgi assembly.
- Hsp90 may act as a general regulator for Rab GTPase recycling across various exocytic and endocytic pathways, impacting cell signaling and proliferation.
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