Vesicle cholesterol controls exocytotic fusion pore

Rituper, Boštjan (avtor), Guček, Alenka (avtor), Lisjak, Marjeta (avtor), Górska, Urszula (avtor), Trkov, Saša (avtor), Lasič, Eva (avtor), Božić, Mićo (avtor), Jorgačevski, Jernej (avtor), Kreft, Marko (avtor), Stenovec, Matjaž (avtor), Božič, Bojan (avtor), Zorec, Robert (avtor)

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 Ca$^{2+}$-dependent exocytosis regulated by distinct Ca$^{2+}$ sources, evokes vesicle secretion. Although this treatment enhanced cytosolic levels of Ca$^{2+}$ 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.

• Jezik: Angleški jezik
• Ključne besede: cholesterol, exocytosis, fusion pore conductance, constriction force, fusion pore widening and constriction, lysosomal storage disease
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: MF - Medicinska fakulteta
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2022
• Št. strani: 17 str.
• Številčenje: Vol. 101, art. 102503
• PID: 20.500.12556/RUL-138888
• UDK: 616-092
• ISSN pri članku: 1532-1991
• DOI: 10.1016/j.ceca.2021.102503
• COBISS.SI-ID: 87034627
• Datum objave v RUL: 24.08.2022

Gradivo je del revije

• Naslov: Cell calcium
• Skrajšan naslov: Cell calcium
• Založnik: Elsevier
• ISSN: 1532-1991
• COBISS.SI-ID: 77488387

Licence

• Licenca: CC BY-NC-ND 4.0, Creative Commons Priznanje avtorstva-Nekomercialno-Brez predelav 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by-nc-nd/4.0/deed.sl
• Opis: Najbolj omejujoča licenca Creative Commons. Uporabniki lahko prenesejo in delijo delo v nekomercialne namene in ga ne smejo uporabiti za nobene druge namene.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: holesterol, eksocitoza, prevodnost fuzijskih por