http://www.cnr.it/ontology/cnr/individuo/prodotto/ID38756

Cholesterol reduction impairs exocytosis of synaptic vesicles. (Articolo in rivista)

Type

Prodotto della ricerca (Classe)
Articolo in rivista (Classe)

Label

Cholesterol reduction impairs exocytosis of synaptic vesicles. (Articolo in rivista) (literal)

Anno

2010-01-01T00:00:00+01:00 (literal)

Alternative label

Linetti A1, Fratangeli A1, Taverna E1, Valnegri P1, Francolini M1,2, Cappello V1, Matteoli M1,2, Passafaro M1,3 and Rosa P1 (2010)
Cholesterol reduction impairs exocytosis of synaptic vesicles.
in Journal of cell science
(literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

Linetti A1, Fratangeli A1, Taverna E1, Valnegri P1, Francolini M1,2, Cappello V1, Matteoli M1,2, Passafaro M1,3 and Rosa P1 (literal)

Pagina inizio

595 (literal)

Pagina fine

605 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume

123 (literal)

Rivista

Journal of cell science (Rivista)

Note

ISI Web of Science (WOS) (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni

1CNR-Institute of Neuroscience, Department of Medical Pharmacology, University of Milan, 20129 Milan, Italy 2IRCCS Fondazione Don Gnocchi, 20149, Milan, Italy 3DTI, Dulbecco Telethon Institute, 20129, Milan, Italy (literal)

Titolo

Cholesterol reduction impairs exocytosis of synaptic vesicles. (literal)

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 Cav2.1channels) in the lipid microdomains of cultured neurons, and then incubated the neurons with fumonisin B (an inhibitor of sphingolipidsynthesis), or with mevastatin or zaragozic acid (two compounds that affect the synthesis of cholesterol by inhibiting HMG-CoAreductase or squalene synthase). The results demonstrate that fumonisin B and zaragozic acid efficiently decrease sphingolipid andcholesterol 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 thoseobserved 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 post-depolarisation increase in fluorescence intensity. Taken together, these findings show that reduced cholesterol levels impair synaptic vesicle exocytosis in cultured neurons. (literal)

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