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Gα13 and Rho mediate endosomal trafficking of CXCR4 into Rab11+ vesicles upon stromal cell-derived factor-1
Ashok Kumar1, Kimberly N Kremer, Daniel Dominguez
1Department of Immunology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|December 15, 2010
Summary
This study reveals a new role for Gα13 proteins in guiding CXCR4 receptor trafficking within T cells. Gα13 and Rho mediate actin polymerization, directing CXCR4 to recycling endosomes containing TCR.
Area of Science:
- Cell Biology
- Molecular Biology
- Immunology
Background:
- G protein-coupled receptors (GPCRs), such as CXCR4, regulate cellular functions via G protein signaling.
- Previous work demonstrated CXCR4 and T cell receptor (TCR) heterodimerization upon stimulation, prolonging ERK activation.
- The intracellular localization and trafficking mechanisms of CXCR4-TCR heterodimers remained unclear.
Purpose of the Study:
- To elucidate the molecular mechanisms governing the post-endocytic trafficking of CXCR4.
- To identify the role of G proteins, specifically Gα13, in CXCR4 receptor trafficking.
- To understand the trafficking pathway of CXCR4-TCR heterodimers.
Main Methods:
- Stimulation of human T cells with stromal cell-derived factor-1 (SDF-1/CXCL12).
- Confocal microscopy to track the localization of CXCR4 and TCR.
- Inhibition of Rho activation and depletion of Gα13 to assess their role in trafficking.
- Analysis of CXCR4 ubiquitination sites and C-terminal tail domain function.
Main Results:
- CXCR4 traffics to Rab11-positive recycling endosomes upon SDF-1 stimulation, requiring its C-terminal tail.
- TCR also localizes to these Rab11-positive compartments, where CXCR4-TCR heterodimers are found.
- Actin polymerization, mediated by Gα13 and Rho, is essential for CXCR4 trafficking into Rab11(+) endosomes.
Conclusions:
- Gα13 and Rho are critical mediators of actin polymerization required for CXCR4 trafficking to Rab11(+) recycling endosomes.
- This pathway facilitates the co-trafficking of CXCR4-TCR heterodimers within T cells.
- This study identifies a novel role for Gα13 in regulating GPCR trafficking.
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