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Identification of an alternative G{alpha}q-dependent chemokine receptor signal transduction pathway in dendritic cells and granulocytes

Shi, Guixiu and Partida-Sánchz, Santiago and Misra, Ravi S. and Tighe, Michael and Borchers, Michael T. and Lee, James J. and Simon, Melvin I. and Lund, Frances E. (2007) Identification of an alternative G{alpha}q-dependent chemokine receptor signal transduction pathway in dendritic cells and granulocytes. Journal of Experimental Medicine, 204 (11). pp. 2705-2718. ISSN 0022-1007. PMCID PMC2118484. https://resolver.caltech.edu/CaltechAUTHORS:SHIjem07

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Abstract

CD38 controls the chemotaxis of leukocytes to some, but not all, chemokines, suggesting that chemokine receptor signaling in leukocytes is more diverse than previously appreciated. To determine the basis for this signaling heterogeneity, we examined the chemokine receptors that signal in a CD38-dependent manner and identified a novel "alternative" chemokine receptor signaling pathway. Similar to the "classical" signaling pathway, the alternative chemokine receptor pathway is activated by G{alpha}i2-containing Gi proteins. However, unlike the classical pathway, the alternative pathway is also dependent on the Gq class of G proteins. We show that G{alpha}q-deficient neutrophils and dendritic cells (DCs) make defective calcium and chemotactic responses upon stimulation with N-formyl methionyl leucyl phenylalanine and CC chemokine ligand (CCL) 3 (neutrophils), or upon stimulation with CCL2, CCL19, CCL21, and CXC chemokine ligand (CXCL) 12 (DCs). In contrast, G{alpha}q-deficient T cell responses to CXCL12 and CCL19 remain intact. Thus, the alternative chemokine receptor pathway controls the migration of only a subset of cells. Regardless, the novel alternative chemokine receptor signaling pathway appears to be critically important for the initiation of inflammatory responses, as G{alpha}q is required for the migration of DCs from the skin to draining lymph nodes after fluorescein isothiocyanate sensitization and the emigration of monocytes from the bone marrow into inflamed skin after contact sensitization.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1084/jem.20071267DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118484/PubMed CentralArticle
Additional Information:© 2007 The Rockefeller University Press. Submitted: 21 June 2007. Accepted: 25 September 2007. Published online 15 October 2007. We thank Dr. Troy Randall for critically evaluating this manuscript and Dr. Tim Walseth for providing us with the 8Br-cADPR used in this study. This work was supported by the Trudeau Institute and National Institutes of Health grant AI-057996. The authors have no conflicting financial interests. G. Shi and S. Partida-Sánchez contributed equally to this work.
Funders:
Funding AgencyGrant Number
Trudeau InstituteUNSPECIFIED
NIHAI-057996
Issue or Number:11
PubMed Central ID:PMC2118484
Record Number:CaltechAUTHORS:SHIjem07
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:SHIjem07
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:9261
Collection:CaltechAUTHORS
Deposited By: Archive Administrator
Deposited On:03 Dec 2007
Last Modified:08 Jul 2020 22:01

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