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First published online April 23, 2007

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Rho-bust chemokine receptor sorting

Chemokines stimulate immune responses by attracting and activating white blood cells. They bind to receptors such as CXCR2, inducing signalling and clathrin-mediated endocytosis of the receptor. After short-term stimulation, CXCR2 recycles to the plasma membrane via recycling compartments; after long-term stimulation, it instead moves into lysosomes for degradation. But what controls this sorting decision? Part of the answer, report Ann Richmond and co-workers on p. 1559, is the small GTPase RhoB. The authors show that expression of a dominant-negative RhoB (T19N) mutant or knocking down RhoB by RNAi impairs CXCR2-mediated chemotaxis and sorting of CXCR2 to lysosomes after long-term stimulation. By contrast, expression of an activated RhoB (Q63L) mutant (which also inhibits chemotaxis and CXCR2 degradation) impairs receptor recycling through the normal (Rab11a-positive) recycling compartment after short-term stimulation, they report, and makes CXCR2 cycle through alternative pathways. The authors propose, therefore, that the RhoB GTPase activity plays an essential role in determining the differential sorting decisions that optimise CXCR2 trafficking and, consequently, chemotaxis.

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Related articles in JCS:

RhoB plays an essential role in CXCR2 sorting decisions

Nicole F. Neel, Lynne A. Lapierre, James R. Goldenring, and Ann Richmond
JCS 2007 120: 1559-1571. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?