Cholesterol modulates acetylcholine receptor diffusion by tuning confinement sojourns and nanocluster stability.

Abstract:

:Translational motion of neurotransmitter receptors is key for determining receptor number at the synapse and hence, synaptic efficacy. We combine live-cell STORM superresolution microscopy of nicotinic acetylcholine receptor (nAChR) with single-particle tracking, mean-squared displacement (MSD), turning angle, ergodicity, and clustering analyses to characterize the lateral motion of individual molecules and their collective behaviour. nAChR diffusion is highly heterogeneous: subdiffusive, Brownian and, less frequently, superdiffusive. At the single-track level, free walks are transiently interrupted by ms-long confinement sojourns occurring in nanodomains of ~36 nm radius. Cholesterol modulates the time and the area spent in confinement. Turning angle analysis reveals anticorrelated steps with time-lag dependence, in good agreement with the permeable fence model. At the ensemble level, nanocluster assembly occurs in second-long bursts separated by periods of cluster disassembly. Thus, millisecond-long confinement sojourns and second-long reversible nanoclustering with similar cholesterol sensitivities affect all trajectories; the proportion of the two regimes determines the resulting macroscopic motional mode and breadth of heterogeneity in the ensemble population.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Mosqueira A,Camino PA,Barrantes FJ

doi

10.1038/s41598-018-30384-y

subject

Has Abstract

pub_date

2018-08-10 00:00:00

pages

11974

issue

1

issn

2045-2322

pii

10.1038/s41598-018-30384-y

journal_volume

8

pub_type

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