Boštjan Rituper (Avtor), Alenka Guček (Avtor), Marjeta Lisjak (Avtor), Urszula Górska (Avtor), Aleksandra Šakanović (Avtor), Saša Trkov (Avtor), Eva Lasič (Avtor), Mićo Božić (Avtor), Jernej Jorgačevski (Avtor), Marko Kreft (Avtor), Alexei Verkhratsky (Avtor), Gregor Anderluh (Avtor), Matjaž Stenovec (Avtor), Bojan Božič (Avtor), Robert Zorec (Avtor)

Povzetek

In some lysosomal storage diseases (LSD) cholesterol accumulates in vesicles. Whether increased vesicle cholesterol affects vesicle fusion with the plasmalemma, where the fusion pore, a channel between the vesicle lumen and the extracellular space, is formed, is unknown. Super-resolution microscopy revealed that after stimulation of exocytosis, pituitary lactotroph vesicles discharge cholesterol which transfers to the plasmalemma. Cholesterol depletion in lactotrophs and astrocytes, both exhibiting Ca2+-dependent exocytosis regulated by distinct Ca2+sources, evokes vesicle secretion. Although this treatment enhanced cytosolic levels of Ca2+ in lactotrophs but decreased it in astrocytes, this indicates that cholesterol may well directly define the fusion pore. In an attempt to explain this mechanism, a new model of cholesterol-dependent fusion pore regulation is proposed. High-resolution membrane capacitance measurements, used to monitor fusion pore conductance, a parameter related to fusion pore diameter, confirm that at resting conditions reducing cholesterol increases, while enrichment with cholesterol decreases the conductance of the fusion pore. In resting fibroblasts, lacking the Npc1 protein, a cellular model of LSD in which cholesterol accumulates in vesicles, the fusion pore conductance is smaller than in controls, showing that vesicle cholesterol controls fusion pore and is relevant for pathophysiology of LSD.

Ključne besede

cholesterol;exocytosis;fusion pore conductance;

Podatki

Jezik: Angleški jezik
Leto izida:
Tipologija: 1.01 - Izvirni znanstveni članek
Organizacija: UL MF - Medicinska fakulteta
UDK: 616-092
COBISS: 87034627 Povezava se bo odprla v novem oknu
ISSN: 1532-1991
Št. ogledov: 189
Št. prenosov: 59
Ocena: 0 (0 glasov)
Metapodatki: JSON JSON-RDF JSON-LD TURTLE N-TRIPLES XML RDFA MICRODATA DC-XML DC-RDF RDF

Ostali podatki

Sekundarni jezik: Slovenski jezik
Sekundarne ključne besede: holesterol;eksocitoza;prevodnost fuzijskih por;
Vrsta dela (COBISS): Članek v reviji
Strani: str. 1-17
Zvezek: ǂVol. ǂ101
Čas izdaje: 2022
DOI: 10.1016/j.ceca.2021.102503
ID: 16261721