Cited by 210Cellular transport and secretionNeuroscience and Neuropharmacology ResearchLipid Membrane Structure and Behavior

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Cholesterol reduction impairs exocytosis of synaptic vesicles

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Linetti, Anna, Fratangeli, Alessandra, Taverna, Elena, Valnegri, Pamela, Francolini, Maura, Cappello, Valentina, Matteoli, Michela, Passafaro, Maria, Rosa, Patrizia·2010·Journal of Cell Science

DOI 10.1242/jcs.060681

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Abstract

Cholesterol and sphingolipids are abundant in neuronal membranes, where they help the organisation of the membrane microdomains involved in major roles such as axonal and dendritic growth, and synapse and spine stability. The aim of this study was to analyse their roles in presynaptic physiology. We first confirmed the presence of proteins of the exocytic machinery (SNARES and Ca(v)2.1 channels) in the lipid microdomains of cultured neurons, and then incubated the neurons with fumonisin B (an inhibitor of sphingolipid synthesis), or with mevastatin or zaragozic acid (two compounds that affect the synthesis of cholesterol by inhibiting HMG-CoA reductase or squalene synthase). The results demonstrate that fumonisin B and zaragozic acid efficiently decrease sphingolipid and cholesterol levels without greatly affecting the viability of neurons or the expression of synaptic proteins. Electron microscopy showed that the morphology and number of synaptic vesicles in the presynaptic boutons of cholesterol-depleted neurons were similar to those observed in control neurons. Zaragozic acid (but not fumonisin B) treatment impaired synaptic vesicle uptake of the lipophilic dye FM1-43 and an antibody directed against the luminal epitope of synaptotagmin-1, effects that depended on the reduction in cholesterol because they were reversed by cholesterol reloading. The time-lapse confocal imaging of neurons transfected with ecliptic SynaptopHluorin showed that cholesterol depletion affects the…

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Authors: Linetti, A., Fratangeli, A., Taverna, E., Valnegri, P., Francolini, M., Cappello, V., Matteoli, M., Passafaro, M., & Rosa, P.
Affiliations: University of Milan (IT)
Corresponding author: Rosa, Patrizia
ORCID: Taverna, Elena
Francolini, Maura
Cappello, Valentina
Matteoli, Michela
Passafaro, Maria
Rosa, Patrizia
Venue: Journal of Cell Science
Publisher: The Company of Biologists
Published: 2010-02-15
Volume: 123
Issue: 4
Pages: 595-605
ISSN: 0021-9533 (ISSN-L)
1477-9137
DOI: 10.1242/jcs.060681
OpenAlex: W2160339294
Cited by: 209
References: 53
Citations by year: 2026: 6 · 2025: 16 · 2024: 13 · 2023: 14 · 2022: 15 · 2021: 12 · 2020: 17 · 2019: 15 · 2018: 13 · 2017: 11 · 2016: 11 · 2015: 14 · 2014: 19 · 2013: 16 · 2012: 5
FWCI: 4.61
Type: journal article
Language: en
Open access: green
zenodo.org
Licence: cc-by
Locations: Journal of Cell Science (publishedVersion)
PubMed (publishedVersion)
INFM-OAR (INFN Catania) (submittedVersion, cc-by)
Funders: Compagnia di San Paolo (2005.1964)
Università degli Studi di Milano
Fondazione Cariplo
Ministero dell’Istruzione, dell’Università e della Ricerca
Consiglio Nazionale delle Ricerche
Università degli Studi di Genova
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
Keywords: cholesterol, sphingolipids, synaptic vesicle exocytosis, presynaptic terminals, lipid rafts, fumonisin B, zaragozic acid, mevastatin, HMG-CoA reductase inhibition, squalene synthase inhibition, SNARE proteins, synaptotagmin-1, cholesterol depletion
MeSH terms: Animals, Anticholesteremic Agents, Cells, Cultured, Cholesterol, Exocytosis, Immunoglobulin G, Lovastatin, Models, Neurological, Neurons, Sphingolipids, Synaptic Vesicles, Tricarboxylic Acids, Presynaptic Terminals, Bridged Bicyclo Compounds, Heterocyclic, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Calcium Channels, N-Type, Membrane Microdomains, Fumonisins, Microscopy, Electron, Transmission, SNARE Proteins, Synaptotagmin I, Rats

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Cholesterol reduction impairs exocytosis of synaptic vesicles

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