Megalencephalic leukoencephalopathy with subcortical cysts protein-1: A new calcium-sensitive protein functionally activated by endoplasmic reticulum calcium release and calmodulin binding in astrocytes.
Astrogliosis
CCE
CaM
CaMKII
EGFR
ER Ca(2+) release
Leukodystrophy
Rare diseases
Regulatory volume decrease
VRAC
Journal
Neurobiology of disease
ISSN: 1095-953X
Titre abrégé: Neurobiol Dis
Pays: United States
ID NLM: 9500169
Informations de publication
Date de publication:
21 Dec 2023
21 Dec 2023
Historique:
received:
23
06
2023
revised:
04
12
2023
accepted:
18
12
2023
medline:
24
12
2023
pubmed:
24
12
2023
entrez:
23
12
2023
Statut:
aheadofprint
Résumé
MLC1 is a membrane protein highly expressed in brain perivascular astrocytes and whose mutations account for the rare leukodystrophy (LD) megalencephalic leukoencephalopathy with subcortical cysts disease (MLC). MLC is characterized by macrocephaly, brain edema and cysts, myelin vacuolation and astrocyte swelling which cause cognitive and motor dysfunctions and epilepsy. In cultured astrocytes, lack of functional MLC1 disturbs cell volume regulation by affecting anion channel (VRAC) currents and the consequent regulatory volume decrease (RVD) occurring in response to osmotic changes. Moreover, MLC1 represses intracellular signaling molecules (EGFR, ERK1/2, NF-kB) inducing astrocyte activation and swelling following brain insults. Nevertheless, to date, MLC1 proper function and MLC molecular pathogenesis are still elusive. We recently reported that in astrocytes MLC1 phosphorylation by the Ca We used U251 astrocytoma cells stably expressing wild-type (WT) or mutated MLC1, primary mouse astrocytes and mouse brain tissue, and applied biochemistry, molecular biology, video imaging and electrophysiology techniques. We revealed that WT but not mutant MLC1 oligomerization and trafficking to the astrocyte plasma membrane is favored by Ca Overall, we qualified MLC1 as a Ca
Sections du résumé
BACKGROUND
BACKGROUND
MLC1 is a membrane protein highly expressed in brain perivascular astrocytes and whose mutations account for the rare leukodystrophy (LD) megalencephalic leukoencephalopathy with subcortical cysts disease (MLC). MLC is characterized by macrocephaly, brain edema and cysts, myelin vacuolation and astrocyte swelling which cause cognitive and motor dysfunctions and epilepsy. In cultured astrocytes, lack of functional MLC1 disturbs cell volume regulation by affecting anion channel (VRAC) currents and the consequent regulatory volume decrease (RVD) occurring in response to osmotic changes. Moreover, MLC1 represses intracellular signaling molecules (EGFR, ERK1/2, NF-kB) inducing astrocyte activation and swelling following brain insults. Nevertheless, to date, MLC1 proper function and MLC molecular pathogenesis are still elusive. We recently reported that in astrocytes MLC1 phosphorylation by the Ca
METHODS
METHODS
We used U251 astrocytoma cells stably expressing wild-type (WT) or mutated MLC1, primary mouse astrocytes and mouse brain tissue, and applied biochemistry, molecular biology, video imaging and electrophysiology techniques.
RESULTS
RESULTS
We revealed that WT but not mutant MLC1 oligomerization and trafficking to the astrocyte plasma membrane is favored by Ca
CONCLUSION
CONCLUSIONS
Overall, we qualified MLC1 as a Ca
Identifiants
pubmed: 38141856
pii: S0969-9961(23)00404-7
doi: 10.1016/j.nbd.2023.106388
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
106388Informations de copyright
Copyright © 2023. Published by Elsevier Inc.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare no conflict of interest.