Development/Plasticity/Repair Lateral Mobility of Nicotinic Acetylcholine Receptors on Neurons Is Determined by Receptor Composition, Local Domain, and Cell Type

The 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 3-containing receptors (3*-nAChRs) and homopentameric 7-containing receptors (7-nAChRs) access synaptic domains by lateral diffusion. They have comparablemobilities and display Brownian motion in extrasynaptic space but are constrained andmovemore slowly in synaptic space. The two receptor types differ in the nature of their synaptic restraints.Disruptionof lipid rafts, PDZ-containing scaffolds, andactin filaments each increase themobility of7-nAChRs in synaptic space while collapse ofmicrotubules has no effect. The opposite is seen for3*-nAChRswhere synapticmobility is increased only bymicrotubule collapse and not the othermanipulations. Other differences are found for regulation of3*-nAChR and7-nAChR mobilities in extrasynaptic space. Most striking are effects on the immobile populations of7-nAChRs and3*-nAChRs. Disruption of either lipid rafts or PDZ scaffolds renders half of the immobile 3*-nAChRs mobile without changing the proportion of immobile 7-nAChRs. Similar resultswere obtainedwith chick sympathetic ganglionneurons, though regulationof receptormobility differed in at least one respect fromthat seenwith ciliary ganglionneurons.Control of nAChR lateralmobility, therefore, is determinedbymechanisms 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