title: Lateral mobility of nicotinic acetylcholine receptors on neurons is determined by receptor composition, local domain, and cell type.
abstract: 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 alpha3-containing receptors (alpha3*-nAChRs) and homopentameric alpha7-containing receptors (alpha7-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 alpha7-nAChRs in synaptic space while collapse of microtubules has no effect. The opposite is seen for alpha3*-nAChRs where synaptic mobility is increased only by microtubule collapse and not the other manipulations. Other differences are found for regulation of alpha3*-nAChR and alpha7-nAChR mobilities in extrasynaptic space. Most striking are effects on the immobile populations of alpha7-nAChRs and alpha3*-nAChRs. Disruption of either lipid rafts or PDZ scaffolds renders half of the immobile alpha3*-nAChRs mobile without changing the proportion of immobile alpha7-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.
authors.affiliation: Neurobiology Section, Division of Biological Sciences, University of California, San Diego, La Jolla, California 92093-0357, USA.
authors.forename: Catarina C
authors.initials: CC
authors.lastname: Fernandes
authors.forename: Darwin K
authors.initials: DK
authors.lastname: Berg
authors.forename: David
authors.initials: D
authors.lastname: Gómez-Varela
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D002784:Cholesterol / Q000378:metabolism; D004058:Diffusion; D005726:Ganglia, Parasympathetic / Q000378:metabolism; D005728:Ganglia, Sympathetic / Q000378:metabolism; D021962:Membrane Microdomains / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D009038:Motion; D009474:Neurons / Q000378:metabolism*; D054731:PDZ Domains; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: D002784:Cholesterol; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor