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MLC1 protein: a likely link between leukodystrophies and brain channelopathies

Megalencephalic leukoencephalopathy with subcortical cysts (MLCs) disease is a rare inherited, autosomal recessive form of childhood-onset spongiform leukodystrophy characterized by macrocephaly, deterioration of motor functions, epileptic seizures and mental decline. Brain edema, subcortical fluid...

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Autores principales: Brignone, Maria S., Lanciotti, Angela, Camerini, Serena, De Nuccio, Chiara, Petrucci, Tamara C., Visentin, Sergio, Ambrosini, Elena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4381631/
https://www.ncbi.nlm.nih.gov/pubmed/25883547
http://dx.doi.org/10.3389/fncel.2015.00106
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author Brignone, Maria S.
Lanciotti, Angela
Camerini, Serena
De Nuccio, Chiara
Petrucci, Tamara C.
Visentin, Sergio
Ambrosini, Elena
author_facet Brignone, Maria S.
Lanciotti, Angela
Camerini, Serena
De Nuccio, Chiara
Petrucci, Tamara C.
Visentin, Sergio
Ambrosini, Elena
author_sort Brignone, Maria S.
collection PubMed
description Megalencephalic leukoencephalopathy with subcortical cysts (MLCs) disease is a rare inherited, autosomal recessive form of childhood-onset spongiform leukodystrophy characterized by macrocephaly, deterioration of motor functions, epileptic seizures and mental decline. Brain edema, subcortical fluid cysts, myelin and astrocyte vacuolation are the histopathological hallmarks of MLC. Mutations in either the MLC1 gene (>75% of patients) or the GlialCAM gene (<20% of patients) are responsible for the disease. Recently, the GlialCAM adhesion protein was found essential for the membrane expression and function of the chloride channel ClC-2 indicating MLC disease caused by mutation in GlialCAM as the first channelopathy among leukodystrophies. On the contrary, the function of MLC1 protein, which binds GlialCAM, its functional relationship with ClC-2 and the molecular mechanisms underlying MLC1 mutation-induced functional defects are not fully understood yet. The human MLC1 gene encodes a 377-amino acid membrane protein with eight predicted transmembrane domains which shows very low homology with voltage-dependent potassium (K(+)) channel subunits. The high expression of MLC1 in brain astrocytes contacting blood vessels and meninges and brain alterations observed in MLC patients have led to hypothesize a role for MLC1 in the regulation of ion and water homeostasis. Recent studies have shown that MLC1 establishes structural and/or functional interactions with several ion/water channels and transporters and ion channel accessory proteins, and that these interactions are affected by MLC1 mutations causing MLC. Here, we review data on MLC1 functional properties obtained in in vitro and in vivo models and discuss evidence linking the effects of MLC1 mutations to brain channelopathies.
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spelling pubmed-43816312015-04-16 MLC1 protein: a likely link between leukodystrophies and brain channelopathies Brignone, Maria S. Lanciotti, Angela Camerini, Serena De Nuccio, Chiara Petrucci, Tamara C. Visentin, Sergio Ambrosini, Elena Front Cell Neurosci Neuroscience Megalencephalic leukoencephalopathy with subcortical cysts (MLCs) disease is a rare inherited, autosomal recessive form of childhood-onset spongiform leukodystrophy characterized by macrocephaly, deterioration of motor functions, epileptic seizures and mental decline. Brain edema, subcortical fluid cysts, myelin and astrocyte vacuolation are the histopathological hallmarks of MLC. Mutations in either the MLC1 gene (>75% of patients) or the GlialCAM gene (<20% of patients) are responsible for the disease. Recently, the GlialCAM adhesion protein was found essential for the membrane expression and function of the chloride channel ClC-2 indicating MLC disease caused by mutation in GlialCAM as the first channelopathy among leukodystrophies. On the contrary, the function of MLC1 protein, which binds GlialCAM, its functional relationship with ClC-2 and the molecular mechanisms underlying MLC1 mutation-induced functional defects are not fully understood yet. The human MLC1 gene encodes a 377-amino acid membrane protein with eight predicted transmembrane domains which shows very low homology with voltage-dependent potassium (K(+)) channel subunits. The high expression of MLC1 in brain astrocytes contacting blood vessels and meninges and brain alterations observed in MLC patients have led to hypothesize a role for MLC1 in the regulation of ion and water homeostasis. Recent studies have shown that MLC1 establishes structural and/or functional interactions with several ion/water channels and transporters and ion channel accessory proteins, and that these interactions are affected by MLC1 mutations causing MLC. Here, we review data on MLC1 functional properties obtained in in vitro and in vivo models and discuss evidence linking the effects of MLC1 mutations to brain channelopathies. Frontiers Media S.A. 2015-04-01 /pmc/articles/PMC4381631/ /pubmed/25883547 http://dx.doi.org/10.3389/fncel.2015.00106 Text en Copyright © 2015 Brignone, Lanciotti, Camerini, De Nuccio, Petrucci, Visentin and Ambrosini. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Brignone, Maria S.
Lanciotti, Angela
Camerini, Serena
De Nuccio, Chiara
Petrucci, Tamara C.
Visentin, Sergio
Ambrosini, Elena
MLC1 protein: a likely link between leukodystrophies and brain channelopathies
title MLC1 protein: a likely link between leukodystrophies and brain channelopathies
title_full MLC1 protein: a likely link between leukodystrophies and brain channelopathies
title_fullStr MLC1 protein: a likely link between leukodystrophies and brain channelopathies
title_full_unstemmed MLC1 protein: a likely link between leukodystrophies and brain channelopathies
title_short MLC1 protein: a likely link between leukodystrophies and brain channelopathies
title_sort mlc1 protein: a likely link between leukodystrophies and brain channelopathies
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4381631/
https://www.ncbi.nlm.nih.gov/pubmed/25883547
http://dx.doi.org/10.3389/fncel.2015.00106
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