Lateral mobility of nicotinic acetylcholine receptors on neurons is determined by receptor composition, local domain, and cell type

Copyright © 2010 the authorsThe lateral mobility of surface receptors can define the signaling properties of a synapse and rapidly change synaptic function. Here we use single-particle tracking with Quantum Dots to follow nicotinic acetylcholine receptors (nAChRs) on the surface of chick ciliary ganglion neurons in culture. We find that both heteropentameric α3-containing receptors (α3*-nAChRs) and homopentameric α7-containing receptors (α7-nAChRs) access synaptic domains by lateral diffusion. They have comparable mobilities and display Brownian motion in extrasynaptic space but are constrained and move more slowly in synaptic space. The two receptor types differ in the nature of their synaptic restraints. Disruption of lipid rafts, PDZ-containing scaffolds, and actin filaments each increase the mobility of α7-nAChRs in synaptic space while collapse of microtubules has no effect. The opposite is seen for α3*-nAChRs where synaptic mobility is increased only by microtubule collapse and not the other manipulations. Other differences are found for regulation of α3*-nAChR and α7-nAChR mobilities in extrasynaptic space. Most striking are effects on the immobile populations of α7-nAChRs and α3*-nAChRs. Disruption of either lipid rafts or PDZ scaffolds renders half of the immobile α3*-nAChRs mobile without changing the proportion of immobile α7-nAChRs. Similar results were obtained with chick sympathetic ganglion neurons, though regulation of receptor mobility differed in at least one respect from that seen with ciliary ganglion neurons. Control of nAChR lateral mobility, therefore, is determined by mechanisms that are domain specific, receptor subtype dependent, and cell-type constrained. The outcome is a system that could tailor nicotinic signaling capabilities to specific needs of individual locations.Grant support was provided by the National Institutes of Health (NS012601, N0S35469, and American Recovery and Reinvestment Act of 2009 stimulus funds) and the Tobacco-Related Disease Research Program (16RT-0167). C.C.F. is a Fundação Calouste Gulbenkian Graduate Fellow; D.G.V. is a Fundación para la Investigación Científica y Técnica Postdoctoral Fellow and a Tobacco-Related Disease Research Program Postdoctoral Fellow