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Investigating Mast Cell Secretory Granules; from Biosynthesis to Exocytosis
Published on: January 26, 2015
RGS-PX1, a GAP for GalphaS and sorting nexin in vesicular trafficking
1Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92093-0651, USA.
Science (New York, N.Y.)
|December 1, 2001
Summary
Regulator of G protein signaling (RGS) proteins modulate cell signaling. A newly identified RGS protein, RGS-PX1, acts as a GTPase-activating protein (GAP) for Galpha(s) and influences vesicular trafficking.
Area of Science:
- Cellular Biology
- Molecular Biology
- Biochemistry
Background:
- Heterotrimeric GTP-binding proteins (G proteins) are crucial signal transducers.
- Regulator of G protein signaling (RGS) proteins regulate G protein signaling duration and amplitude by acting as GTPase-activating proteins (GAPs).
Purpose of the Study:
- To identify and characterize novel RGS proteins involved in G protein signaling.
- To investigate the bifunctional role of RGS-PX1 in both G protein signaling and vesicular trafficking.
Main Methods:
- Protein interaction studies to confirm RGS-PX1 binding to Galpha(s).
- GTPase activity assays to measure the GAP activity of RGS-PX1 on Galpha(s).
- Cell-based assays to assess the effect of RGS-PX1 on epidermal growth factor receptor (EGF receptor) degradation.
Main Results:
- RGS-PX1 was identified as a Galpha(s)-specific GAP.
- The RGS domain of RGS-PX1 directly interacted with Galpha(s) and accelerated its GTP hydrolysis, attenuating Galpha(s)-mediated signaling.
- RGS-PX1 contains a Phox (PX) domain, similar to sorting nexin (SNX) proteins.
- Expression of RGS-PX1 delayed the lysosomal degradation of the EGF receptor.
Conclusions:
- RGS-PX1 possesses a dual function as a Galpha(s)-specific GAP and a protein with sorting nexin-like properties.
- RGS-PX1 may serve as a molecular link between heterotrimeric G protein signaling pathways and vesicular trafficking processes.
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