ArticleCells2020
Megalencephalic Leukoencephalopathy with Subcortical Cysts Disease-Linked MLC1 Protein Favors Gap-Junction Intercellular Communication by Regulating Connexin 43 Trafficking in Astrocytes.
Article in Cells, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- Mitochondrial Transfer in the Neurovascular Unit, Not Only for Energy Rescue: A Systematic Review.Aging and disease · 2024Pooled it
- Neuroglial Pathophysiology of Leukodystrophies.Advances in neurobiology · 2025Review
- Astrocytes: Dissecting Their Diverse Roles in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia.Cells · 2023Review
- Connexin 43: An Interface Connecting Neuroinflammation to Depression.Molecules (Basel, Switzerland) · 2023Review
- The CaMKII/MLC1 Axis Confers CaCells · 2022Article
- Ubr1-induced selective endophagy/autophagy protects against the endosomal and CaCellular and molecular life sciences : CMLS · 2022Article
- Mlc1-Expressing Perivascular Astrocytes Promote Blood-Brain Barrier Integrity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Human iPSC-Derived Astrocytes: A Powerful Tool to Study Primary Astrocyte Dysfunction in the Pathogenesis of Rare Leukodystrophies.International journal of molecular sciences · 2021Review
- Review
- Control of membrane protein homeostasis by a chaperone-like glial cell adhesion molecule at multiple subcellular locations.Scientific reports · 2021Article
- Identification of the GlialCAM interactome: the G protein-coupled receptors GPRC5B and GPR37L1 modulate megalencephalic leukoencephalopathy proteins.Human molecular genetics · 2021Article
- Megalencephalic leukoencephalopathy with subcortical cysts 1 (MLC1) promotes glioblastoma cell invasion in the brain microenvironment.Oncogene · 2020Article
- Megalencephalic Leukoencephalopathy: Insights Into Pathophysiology and Perspectives for Therapy.Frontiers in cellular neuroscience · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Astrocytes, the most numerous cells of the central nervous system, exert critical functions for brain homeostasis. To this purpose, astrocytes generate a highly interconnected intercellular network allowing rapid exchange of ions and metabolites through gap junctions, adjoined channels composed of hexamers of connexin (Cx) proteins, mainly Cx43. Functional alterations of Cxs and gap junctions have been observed in several neuroinflammatory/neurodegenerative diseases. In the rare leukodystrophy megalencephalic leukoencephalopathy with subcortical cysts (MLC), astrocytes show defective control of ion/fluid exchanges causing brain edema, fluid cysts, and astrocyte/myelin vacuolation. MLC is caused by mutations in MLC1, an astrocyte-specific protein of elusive function, and in GlialCAM, a MLC1 chaperon. Both proteins are highly expressed at perivascular astrocyte end-feet and astrocyte-astrocyte contacts where they interact with zonula occludens-1 (ZO-1) and Cx43 junctional proteins. To investigate the possible role of Cx43 in MLC pathogenesis, we studied Cx43 properties in astrocytoma cells overexpressing wild type (WT) MLC1 or MLC1 carrying pathological mutations. Using biochemical and electrophysiological techniques, we found that WT, but not mutated, MLC1 expression favors intercellular communication by inhibiting extracellular-signal-regulated kinase 1/2 (ERK1/2)-mediated Cx43 phosphorylation and increasing Cx43 gap-junction stability. These data indicate MLC1 regulation of Cx43 in astrocytes and Cx43 involvement in MLC pathogenesis, suggesting potential target pathways for therapeutic interventions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.