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 ␣3-containing receptors (␣3*-nAChRs) and homopentameric ␣7-containing receptors (␣7-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 ␣7-nAChRs in synaptic space while collapse of microtubules has no effect. The opposite is seen for ␣3*-nAChRs where synaptic mobility is increased only by microtubule collapse and not the other manipulations. Other differences are found for regulation of ␣3*-nAChR and ␣7-nAChR mobilities in extrasynaptic space. Most striking are effects on the immobile populations of ␣7-nAChRs and ␣3*-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 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.

Regulation of Neuronal Na,K-ATPase by Extracellular Scaffolding Proteins

“…This is also consistent with previous reports based on SPT-QD for several neuronal receptors and transporters, including AMPAR [23,24], mGluR5 [25], nAChRα3 and 7 [26] and KCC2 [27]. …”

Resveratrol induces ordered domains formation in biomembranes: Implication for its pleiotropic action

“…For instance, lipid rafts have been associated to organizing centres for the assembly of apoptotic and signalling molecules involved in cell death [50][51][52][53][54][55]. Moreover, several receptors involved in neurological functions, such as α7 nicotinic acetylcholine receptors, were found to be localized into lipid rafts and the disruption of their lipid structure may result in significant changes and receptors desensitization [56][57][58][59]. Therefore, the confirmation that rafts are targeted and stabilized by resveratrol may justify its several pharmacological activities, such as neuroprotection and cancer chemoprevention, through the regulation of cellular events such as neurotransmitter release, second messenger cascades and cell survival.…”

Lateral Diffusion, Function, and Expression of the Slow Channel Congenital Myasthenia Syndrome αC418W Nicotinic Receptor Mutation with Changes in Lipid Raft Components

“…In addition, it has been proposed that changes in cholesterol levels affect the mechanical properties of plasma membrane through the underlying cytoskeleton (69). Fernandes et al (70) showed that nAChR mobility is subtype specific as cholesterol depletion with M␤CD increased the mobility of neuronal ␣7 nAChRs but not that of ␣3 nAChRs in the central nervous system synapses.…”