CHIP-dependent regulation of the actin cytoskeleton is linked to neuronal cell membrane integrity
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F21%3A00078656" target="_blank" >RIV/00209805:_____/21:00078656 - isvavai.cz</a>
Výsledek na webu
<a href="https://reader.elsevier.com/reader/sd/pii/S2589004221008464?token=0B10DE7E31B6B6EE268C01175EA4B39C40620D932E36BFA6881689A188C482C2924C758C8F184B69C5C9E16357D326C7&originRegion=eu-west-1&originCreation=20210818084421" target="_blank" >https://reader.elsevier.com/reader/sd/pii/S2589004221008464?token=0B10DE7E31B6B6EE268C01175EA4B39C40620D932E36BFA6881689A188C482C2924C758C8F184B69C5C9E16357D326C7&originRegion=eu-west-1&originCreation=20210818084421</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.isci.2021.10287" target="_blank" >10.1016/j.isci.2021.10287</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
CHIP-dependent regulation of the actin cytoskeleton is linked to neuronal cell membrane integrity
Popis výsledku v původním jazyce
CHIP is an E3-ubiquitin ligase that contributes to healthy aging and has been characterized as neuroprotective. To elucidate dominant CHIP-dependent changes in protein steady-state levels in a patient-derived human neuronal model, CHIP function was ablated using gene-editing and an unbiased proteomic analysis conducted to compare knock-out and wild-type isogenic induced pluripotent stem cell (iPSC)-derived cortical neurons. Rather than a broad effect on protein homeostasis, loss of CHIP function impacted on a focused cohort of proteins from actin cytoskeleton signaling and membrane integrity networks. In support of the proteomics, CHIP knockout cells had enhanced sensitivity to induced membrane damage. We conclude that the major readout of CHIP function in cortical neurons derived from iPSC of a patient with elevate α-synuclein, Parkinson's disease and dementia, is the modulation of substrates involved in maintaining cellular "health". Thus, regulation of the actin cytoskeletal and membrane integrity likely contributes to the neuroprotective function(s) of CHIP.
Název v anglickém jazyce
CHIP-dependent regulation of the actin cytoskeleton is linked to neuronal cell membrane integrity
Popis výsledku anglicky
CHIP is an E3-ubiquitin ligase that contributes to healthy aging and has been characterized as neuroprotective. To elucidate dominant CHIP-dependent changes in protein steady-state levels in a patient-derived human neuronal model, CHIP function was ablated using gene-editing and an unbiased proteomic analysis conducted to compare knock-out and wild-type isogenic induced pluripotent stem cell (iPSC)-derived cortical neurons. Rather than a broad effect on protein homeostasis, loss of CHIP function impacted on a focused cohort of proteins from actin cytoskeleton signaling and membrane integrity networks. In support of the proteomics, CHIP knockout cells had enhanced sensitivity to induced membrane damage. We conclude that the major readout of CHIP function in cortical neurons derived from iPSC of a patient with elevate α-synuclein, Parkinson's disease and dementia, is the modulation of substrates involved in maintaining cellular "health". Thus, regulation of the actin cytoskeletal and membrane integrity likely contributes to the neuroprotective function(s) of CHIP.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
10608 - Biochemistry and molecular biology
Návaznosti výsledku
Projekt
Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.
Návaznosti
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Ostatní
Rok uplatnění
2021
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
iScience
ISSN
2589-0042
e-ISSN
—
Svazek periodika
24
Číslo periodika v rámci svazku
8
Stát vydavatele periodika
US - Spojené státy americké
Počet stran výsledku
27
Strana od-do
102878
Kód UT WoS článku
000686897200065
EID výsledku v databázi Scopus
2-s2.0-85111835516