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Sci. Signal., 27 October 2009
Vol. 2, Issue 94, p. ec345
[DOI: 10.1126/scisignal.294ec345]

EDITORS' CHOICE

Membrane Trafficking A Ready Supply

Elizabeth M. Adler

Science Signaling, AAAS, Washington, DC 20005, USA

CX3CL1 is one of only two known chemokines that has a transmembrane domain, enabling it to mediate leukocyte adhesion to the endothelium. Its abundance at the cell surface depends on both proteolytic cleavage and constitutive trafficking to and from an endocytic compartment. Indeed, it is the only chemokine known to be constitutively internalized. Huang et al. found that internalization of antibody-labeled CX3CL1 was temperature-dependent, suggesting that it involved endocytosis; experiments with a dominant-negative form of dynamin and experiments with siRNA directed against clathrin indicated that its endocytosis was both dynamin- and clathrin-dependent. Antibodies directed against CX3CL1 showed colocalization with antibodies directed against the AP-2 adaptor complex, and mutational analysis indicated that CX3CL1 endocytosis depended on AP-2 binding motifs in the CX3CL1 cytoplasmic tail. Whereas CX3CL1 was present both intracellularly and at the plasma membrane, TACE (tumor necrosis factor-{alpha} converting enzyme) and ADAM10 (a disintegrin and metalloprotease 10), the two metalloproteases that cleave CX3CL1 to release a soluble chemoattractant form, were predominantly localized to the membrane. Dynamin inhibition or mutation of the AP-2 binding motifs stimulated the protease-dependent release of soluble CX3CL1. The authors thus propose that CX3CL1 internalization protects it from proteolytic cleavage and provides a pool of CX3CL1 that could be rapidly mobilized to the membrane on demand.

Y.-W. Huang, P. Su, G. Y. Liu, M. R. Crow, D. Chaukos, H. Yan, L. A. Robinson, Constitutive endocytosis of the chemokine CX3CL1 prevents its degradation by cell surface metalloproteases. J. Biol. Chem. 284, 29644–29653 (2009). [Abstract] [Full Text]

Citation: E. M. Adler, A Ready Supply. Sci. Signal. 2, ec345 (2009).


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