Sci. Signal., 23 August 2011
Receptors CD36 Goes Line Dancing
Nancy R. Gough
Science Signaling, AAAS, Washington, DC 20005, USA
Receptor clustering is a well-accepted mechanism controlling receptor activity and trafficking. Several models for receptor clustering on the cell surface have been proposed, including those based on lipid microdomains (lipid rafts) and those based on regions defined by submembrane cytoskeletal components (fences) (see Zimmerberg and Hess). Jaqaman et al. used single-particle tracking to show that the scavenger receptor CD36 on the surface of primary human macrophages exhibited three types of movement: ~30% linear, ~20% isotropic and unconfined (moving in all directions), and ~55% isotropic and confined. Receptor clustering events in the absence of ligand were more common in the population exhibiting linear trajectories. The linear movement of the receptors was unaffected by conditions that disrupted lipid rafts, but the fraction exhibiting linear movement was reduced by application of drugs that disrupted actin polymerization or myosin activity, implicating the actomyosin cortical cytoskeleton, and by application of drugs that depolymerized microtubules. The same proportion (~30%) of receptors that exhibited linear movement colocalized with microtubules, and linearly moving receptors colocalized with microtubules. After normalizing for effects on receptor density, drugs that disrupted the actomyosin cytoskeleton appeared to reduce clustering by reducing receptor mobility, whereas disrupting microtubules reduced clustering by reducing receptor density. Disruption of the actomyosin cytoskeleton or microtubule polymerization reduced ligand-stimulated internalization and signaling of CD36, suggesting that the cytoskeleton organizes CD36 to maximize responsiveness to ligands.
K. Jaqaman, H. Kuwata, N. Touret, R. Collins, W. S. Trimble, G. Danuser, S. Grinstein, Cytoskeletal control of CD36 diffusion promotes its receptor and signaling function. Cell 146, 593–606 (2011). [Online Journal]
J. Zimmerberg, S. T. Hess, Elongated membrane zones boost interactions of diffusing proteins. Cell 146, 501–503 (2011). [Online Journal]
Citation: N. R. Gough, CD36 Goes Line Dancing. Sci. Signal. 4, ec235 (2011).
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