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Vesicle cholesterol controls exocytotic fusion pore
ID
Rituper, Boštjan
(
Author
),
ID
Guček, Alenka
(
Author
),
ID
Lisjak, Marjeta
(
Author
),
ID
Górska, Urszula
(
Author
),
ID
Trkov, Saša
(
Author
),
ID
Lasič, Eva
(
Author
),
ID
Božić, Mićo
(
Author
),
ID
Jorgačevski, Jernej
(
Author
),
ID
Kreft, Marko
(
Author
),
ID
Stenovec, Matjaž
(
Author
),
ID
Božič, Bojan
(
Author
),
ID
Zorec, Robert
(
Author
), et al.
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https://www.sciencedirect.com/science/article/pii/S0143416021001573
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Abstract
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.
Language:
English
Keywords:
cholesterol
,
exocytosis
,
fusion pore conductance
,
constriction force
,
fusion pore widening and constriction
,
lysosomal storage disease
Work type:
Article
Typology:
1.01 - Original Scientific Article
Organization:
MF - Faculty of Medicine
Publication status:
Published
Publication version:
Version of Record
Year:
2022
Number of pages:
17 str.
Numbering:
Vol. 101, art. 102503
PID:
20.500.12556/RUL-138888
UDC:
616-092
ISSN on article:
1532-1991
DOI:
10.1016/j.ceca.2021.102503
COBISS.SI-ID:
87034627
Publication date in RUL:
24.08.2022
Views:
637
Downloads:
134
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Record is a part of a journal
Title:
Cell calcium
Shortened title:
Cell calcium
Publisher:
Elsevier
ISSN:
1532-1991
COBISS.SI-ID:
77488387
Licences
License:
CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
Link:
http://creativecommons.org/licenses/by-nc-nd/4.0/
Description:
The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.
Secondary language
Language:
Slovenian
Keywords:
holesterol
,
eksocitoza
,
prevodnost fuzijskih por
Projects
Funder:
ARRS - Slovenian Research Agency
Project number:
P3-0310
Name:
Celična fiziologija
Funder:
ARRS - Slovenian Research Agency
Project number:
P1-0055
Name:
Biofizika polimerov, membran, gelov, koloidov in celic
Funder:
ARRS - Slovenian Research Agency
Project number:
J3-4051
Name:
Vloga monomernih GTPaz pri uravnavanju mobilnosti endosomov/lizosomov v astrocitih
Funder:
ARRS - Slovenian Research Agency
Project number:
J3-4146
Name:
Mobilnost sekrecijskih mešičkov in homeostaza kalcija v astrocitih
Funder:
ARRS - Slovenian Research Agency
Project number:
L3-3654
Name:
Simulacija breztežnosti in zmanjšane težnosti: učinki na kardiovaskularni in na mišično-skeletni sistem
Funder:
ARRS - Slovenian Research Agency
Project number:
J3-3632
Name:
Molekularne lastnosti fuzijske pore
Funder:
ARRS - Slovenian Research Agency
Project number:
J3-6790
Name:
Dinamične meritve metabolitov in sekundarnih prenašalcev v posameznem astrocitu v celični kulturi
Funder:
ARRS - Slovenian Research Agency
Project number:
J3-6789
Name:
Patogeni mehanizem podaljšanih heksanukleotidnih ponovitev v genu C9orf72 pri nevrodegeneraciji
Funder:
ARRS - Slovenian Research Agency
Project number:
J3-7605
Name:
Nanofiziologija eksocitoze v zdravih in bolezenskih razmerah
Funder:
Other - Other funder or multiple funders
Funding programme:
CIPKEBIP
Funder:
Other - Other funder or multiple funders
Funding programme:
COST
Acronym:
Nanonet
Funder:
Other - Other funder or multiple funders
Funding programme:
COST
Acronym:
Mouse Ageing
Funder:
Other - Other funder or multiple funders
Funding programme:
COST
Project number:
CM1207
Acronym:
GLISTEN
Funder:
Other - Other funder or multiple funders
Funding programme:
CELSA
Funder:
NHMRC - National Health and Medical Research Council
Project number:
APP1065328
Funder:
Other - Other funder or multiple funders
Funding programme:
Brock University
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