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RGS4 and RGS2 bind coatomer and inhibit COPI association with Golgi membranes and intracellular transport
B M Sullivan1, K J Harrison-Lavoie, V Marshansky
1Renal Unit, Program in Membrane Biology, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA.
Molecular Biology of the Cell
|September 12, 2000
Summary
Regulator of G protein signaling (RGS4) binds to COPI, a protein complex essential for intracellular transport. This interaction inhibits COPI
Area of Science:
- Cell Biology
- Molecular Biology
- Protein Interactions
Background:
- COPI (coatomer protein I) is crucial for intracellular transport and Golgi integrity.
- Regulators of G protein signaling (RGS) proteins are involved in signal transduction pathways.
Purpose of the Study:
- To investigate the interaction between RGS proteins and the COPI complex.
- To determine the functional consequences of RGS protein binding to COPI.
Main Methods:
- Yeast two-hybrid screening to identify interacting proteins.
- In vitro binding assays with recombinant proteins.
- Cellular cofractionation and immunofluorescence studies.
- Functional assays measuring protein trafficking and secretion.
Main Results:
- RGS4 and RGS2 directly bind to the beta'-COP subunit of COPI via dilysine motifs.
- RGS4 inhibits COPI binding to Golgi membranes independently of its GTPase-accelerating activity.
- RGS4 expression reduces Golgi-associated COPI without affecting Golgi integrity or ARF1 levels.
- RGS4 inhibits aquaporin 1 trafficking and placental alkaline phosphatase secretion.
Conclusions:
- RGS proteins can sequester COPI in the cytoplasm, inhibiting its recruitment to Golgi membranes.
- This sequestration modulates intracellular transport pathways, including Golgi-plasma membrane and intra-Golgi transport.
- RGS proteins represent novel regulators of COPI-mediated intracellular trafficking.
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