Identification of an alternative Gαq-dependent chemokine receptor signal transduction pathway in dendritic cells and granulocytes

Guixiu Shi, Santiago Partida-Sánchez, Ravi S. Misra, Michael Tighe, Michael T. Borchers, James J. Lee, Melvin I. Simon, Frances E. Lund

Research output: Contribution to journalArticle

56 Citations (Scopus)

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 Gαi2-containing Gi proteins. However, unlike the classical pathway, the alternative pathway is also dependent on the Gq class of G proteins. We show that Gαq-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, Gαq-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 Gαq 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. JEM

Original languageEnglish (US)
Pages (from-to)2705-2718
Number of pages14
JournalJournal of Experimental Medicine
Volume204
Issue number11
DOIs
StatePublished - Oct 29 2007

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Chemokine Receptors
Granulocytes
Dendritic Cells
Signal Transduction
Neutrophils
Gq-G11 GTP-Binding Protein alpha Subunits
Leukocyte Chemotaxis
Ligands
N-Formylmethionine Leucyl-Phenylalanine
CXC Chemokines
CC Chemokines
Langerhans Cells
Emigration and Immigration
Fluorescein
Chemokines
Monocytes
Leukocytes
Lymph Nodes
Bone Marrow
Calcium

ASJC Scopus subject areas

  • Immunology

Cite this

Shi, G., Partida-Sánchez, S., Misra, R. S., Tighe, M., Borchers, M. T., Lee, J. J., ... Lund, F. E. (2007). Identification of an alternative Gαq-dependent chemokine receptor signal transduction pathway in dendritic cells and granulocytes. Journal of Experimental Medicine, 204(11), 2705-2718. https://doi.org/10.1084/jem.20071267

Identification of an alternative Gαq-dependent chemokine receptor signal transduction pathway in dendritic cells and granulocytes. / Shi, Guixiu; Partida-Sánchez, Santiago; Misra, Ravi S.; Tighe, Michael; Borchers, Michael T.; Lee, James J.; Simon, Melvin I.; Lund, Frances E.

In: Journal of Experimental Medicine, Vol. 204, No. 11, 29.10.2007, p. 2705-2718.

Research output: Contribution to journalArticle

Shi, G, Partida-Sánchez, S, Misra, RS, Tighe, M, Borchers, MT, Lee, JJ, Simon, MI & Lund, FE 2007, 'Identification of an alternative Gαq-dependent chemokine receptor signal transduction pathway in dendritic cells and granulocytes', Journal of Experimental Medicine, vol. 204, no. 11, pp. 2705-2718. https://doi.org/10.1084/jem.20071267
Shi, Guixiu ; Partida-Sánchez, Santiago ; Misra, Ravi S. ; Tighe, Michael ; Borchers, Michael T. ; Lee, James J. ; Simon, Melvin I. ; Lund, Frances E. / Identification of an alternative Gαq-dependent chemokine receptor signal transduction pathway in dendritic cells and granulocytes. In: Journal of Experimental Medicine. 2007 ; Vol. 204, No. 11. pp. 2705-2718.
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