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

Cholesterol reduction impairs exocytosis of synaptic vesicles

Open access
Linetti, Anna, Fratangeli, Alessandra, Taverna, Elena, Valnegri, Pamela, Francolini, Maura, Cappello, Valentina, Matteoli, Michela, Passafaro, Maria +1 more·2010·Journal of Cell Science

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…

Integrity signals

Registry

Crossref · 10.1242/jcs.060681

Cites

53 of 53 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Restoration of membrane lipid rafts might contribute to the beneficial effects of cholesterol supplementation.

    “One mechanism that might contribute to these effects is the restoration of membrane lipid rafts, cholesterol-enriched microdomains that organize signaling molecules and synaptic proteins and are required for efficient synaptic transmission (Korinek et al., 2020;Linetti et al., 2010).”

Cites

Flagged first, then by citations

Cited by

Sorted by citations

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
Venue
Journal of Cell Science
Published
2010-02-15
Volume
123
Issue
4
Pages
595-605
ISSN
  • 0021-9533 (ISSN-L)
  • 1477-9137
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
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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review