ArticleThe Journal of physiology2014
Cholesterol and F-actin are required for clustering of recycling synaptic vesicle proteins in the presynaptic plasma membrane.
Article in The Journal of physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 47 citations in OpenAlex.
- The synaptic vesicle cluster as a controller of pre- and postsynaptic structure and function.The Journal of physiology · 2025Review
- Phospholipid Scramblase 1 Controls Efficient Neurotransmission and Synaptic Vesicle Retrieval at Cerebellar Synapses.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Statins suppress cell-to-cell propagation of α-synuclein by lowering cholesterol.Cell death & disease · 2023Article
- Role of the endoplasmic reticulum in synaptic transmission.Current opinion in neurobiology · 2022Review
- The CD63 homologs, Tsp42Ee and Tsp42Eg, restrict endocytosis and promote neurotransmission through differential regulation of synaptic vesicle pools.Frontiers in cellular neuroscience · 2022Article
- Mutants of theInternational journal of molecular sciences · 2021Article
- Disposition of Proteins and Lipids in Synaptic Membrane Compartments Is Altered in Q175/Q7 Huntington's Disease Mouse Striatum.Frontiers in synaptic neuroscience · 2021Article
- Article
- Cholesterol modulates presynaptic and postsynaptic properties of excitatory synaptic transmission.Scientific reports · 2020Article
- Divalent cations bind to phosphoinositides to induce ion and isomer specific propensities for nano-cluster initiation in bilayer membranes.Royal Society open science · 2020Article
- Statin-mediated cholesterol depletion exerts coordinated effects on the alterations in rat vascular smooth muscle cell biomechanics and migration.The Journal of physiology · 2020Article
- The Cell Biology of Tau Secretion.Frontiers in molecular neuroscience · 2020Review
- MERCs. The Novel Assistant to Neurotransmission?Frontiers in neuroscience · 2020Review
- Reciprocal modulation between amyloid precursor protein and synaptic membrane cholesterol revealed by live cell imaging.Neurobiology of disease · 2019Article
- Cholesterol and the Safety Factor for Neuromuscular Transmission.International journal of molecular sciences · 2019Review
- Cholesterol-loaded nanoparticles ameliorate synaptic and cognitive function in Huntington's disease mice.EMBO molecular medicine · 2015Article
- Diffusional spread and confinement of newly exocytosed synaptic vesicle proteins.Nature communications · 2015Article
- Cholesterol regulates multiple forms of vesicle endocytosis at a mammalian central synapse.Journal of neurochemistry · 2015Article
- Transient assembly of F-actin on the outer mitochondrial membrane contributes to mitochondrial fission.The Journal of cell biology · 2015Article
- Cyclodextrin Alters GABAergic Input to CA1 Pyramidal Cells in Wild-Type But Not in NPC1-Deficient Mice.BioResearch open access · 2015Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Synaptic vesicles (SVs) and their proteins must be recycled for sustained synaptic transmission. We tested the hypothesis that SV cholesterol is required for proper sorting of SV proteins during recycling in live presynaptic terminals. We used the reversible block of endocytosis in the Drosophila temperature-sensitive dynamin mutant shibire-ts1 to trap exocytosed SV proteins, and then examined the effect of experimental treatments on the distribution of these proteins within the presynaptic plasma membrane by confocal microscopy. SV proteins synaptotagmin, vglut and csp were clustered following SV trapping in control experiments but dispersed in samples treated with the cholesterol chelator methyl-β-cyclodextrin to extract SV cholesterol. There was accumulation of phosphatidylinositol (4,5)-bisphosphate (PIP2) in presynaptic terminals following SV trapping and this was reduced following SV cholesterol extraction. Reduced PIP2 accumulation was associated with disrupted accumulation of actin in presynaptic terminals. Similar to vesicular cholesterol extraction, disruption of actin by latrunculin A after SV proteins had been trapped on the plasma membrane resulted in the dispersal of SV proteins and prevented recovery of synaptic transmission due to impaired endocytosis following relief of the endocytic block. Our results demonstrate that vesicular cholesterol is required for aggregation of exocytosed SV proteins in the presynaptic plasma membrane and are consistent with a mechanism involving regulation of PIP2 accumulation and local actin polymerization by cholesterol. Thus, alteration of membrane or SV lipids may affect the ability of synapses to undergo sustained synaptic transmission by compromising the recycling of SV proteins.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.