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...

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Detalles Bibliográficos
Autores principales: Mosqueira, Alejo, Camino, Pablo A., Barrantes, Francisco José
Formato: Artículo
Lenguaje:Inglés
Inglés
Publicado: Nature Research 2019
Materias:
COLESTEROL
MOLECULAS
LIPIDOS
NEUROTRANSMISORES
CEREBRO
TRANSMISIÓN SINAPTICA
Acceso en línea:https://repositorio.uca.edu.ar/handle/123456789/1464
Aporte de:
Repositorio Institucional de la Universidad Católica Argentina (UCA) de Universidad Católica Argentina
id I33-R139123456789-1464
record_format dspace
institution Universidad Católica Argentina
institution_str I-33
repository_str R-139
collection Repositorio Institucional de la Universidad Católica Argentina (UCA)
language Inglés
Inglés
topic COLESTEROL
MOLECULAS
LIPIDOS
NEUROTRANSMISORES
CEREBRO
TRANSMISIÓN SINAPTICA
spellingShingle COLESTEROL
MOLECULAS
LIPIDOS
NEUROTRANSMISORES
CEREBRO
TRANSMISIÓN SINAPTICA
Mosqueira, Alejo
Camino, Pablo A.
Barrantes, Francisco José
Cholesterol modulates acetylcholine receptor diffusion by tuning confinement sojourns and nanocluster stability
topic_facet COLESTEROL
MOLECULAS
LIPIDOS
NEUROTRANSMISORES
CEREBRO
TRANSMISIÓN SINAPTICA
description 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.
format Artículo
author Mosqueira, Alejo
Camino, Pablo A.
Barrantes, Francisco José
author_facet Mosqueira, Alejo
Camino, Pablo A.
Barrantes, Francisco José
author_sort Mosqueira, Alejo
title Cholesterol modulates acetylcholine receptor diffusion by tuning confinement sojourns and nanocluster stability
title_short Cholesterol modulates acetylcholine receptor diffusion by tuning confinement sojourns and nanocluster stability
title_full Cholesterol modulates acetylcholine receptor diffusion by tuning confinement sojourns and nanocluster stability
title_fullStr Cholesterol modulates acetylcholine receptor diffusion by tuning confinement sojourns and nanocluster stability
title_full_unstemmed Cholesterol modulates acetylcholine receptor diffusion by tuning confinement sojourns and nanocluster stability
title_sort cholesterol modulates acetylcholine receptor diffusion by tuning confinement sojourns and nanocluster stability
publisher Nature Research
publishDate 2019
url https://repositorio.uca.edu.ar/handle/123456789/1464
work_keys_str_mv AT mosqueiraalejo cholesterolmodulatesacetylcholinereceptordiffusionbytuningconfinementsojournsandnanoclusterstability
AT caminopabloa cholesterolmodulatesacetylcholinereceptordiffusionbytuningconfinementsojournsandnanoclusterstability
AT barrantesfranciscojose cholesterolmodulatesacetylcholinereceptordiffusionbytuningconfinementsojournsandnanoclusterstability
bdutipo_str Repositorios
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