Expression patterns of MLC1 protein in the central and peripheral nervous systems

Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona and Institute for Research in Biomedicine, Barcelona Science Park, Josep Samitier 1-5. Barcelona, E-08028, Spain.
Neurobiology of Disease (Impact Factor: 5.08). 07/2007; 26(3):532-45. DOI: 10.1016/j.nbd.2007.01.016
Source: PubMed


Mutations in MLC1 cause megalencephalic leukoencephalopathy with subcortical cysts (MLC), a disorder characterized clinically by macrocephaly, deterioration of motor functions, epilepsy and mental decline. Recent studies have detected MLC1 mRNA and protein in astroglial processes. In addition, our group previously reported MLC1 expression in some neurons in the adult mouse brain. Here we performed an exhaustive study of the expression pattern of MLC1 in the developing mouse brain by means of optic and electron microscopy. In the central nervous system, MLC1 was detected mainly in axonal tracts early in development. In addition, MLC1 was also observed in the peripheral nervous system and in several sensory epithelia, as retina or saccula maculae. Post-embedding immunogold experiments indicated that MLC1 is localized in astrocyte-astrocyte junctions, but not in the perivascular membrane, indicating that MLC1 is not a component of the dystrophin-glycoprotein complex. In neurons, MLC1 is located at the plasma membrane and vesicular structures. Our data provide a mouse MLC1 expression map that could be useful to understand the phenotype of MLC patients, and suggested that MLC disease is caused by an astrocytic and a neuronal dysfunction.

  • Source
    • "expressed mainly in astrocyte junctions (Teijido et al. 2007; Duarri et al. 2011). Searching for MLC1 binding proteins to identify candidate genes underlying MLC in patients without mutations in MLC1, GlialCAM was identified as a major MLC1 interaction partner; mutations in GLIALCAM result in MLC (Lopez-Hernandez et al. 2011a). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Mutations in the genes encoding the astrocytic protein MLC1, the cell adhesion molecule GlialCAM or the Cl(-) channel ClC-2 underlie human leukodystrophies. GlialCAM binds to itself, to MLC1 and to ClC-2, and directs these proteins to cell-cell contacts. In addition, GlialCAM dramatically activates ClC-2 mediated currents. Here, we used mutagenesis studies combined with functional and biochemical analyses to determine which parts of GlialCAM are needed to perform these cellular functions. We found that the extracellular domain of GlialCAM is necessary for cell junction targeting and for mediating interactions with itself or with MLC1 and ClC-2. The C-terminus is also necessary for proper targeting to cell-cell junctions, but is not needed for the biochemical interaction. Finally, we identified the first three amino acids of the transmembrane segment of GlialCAM as being essential for the activation of ClC-2 currents but not for targeting or biochemical interaction. Our results provide new information to understand the mechanistic insights of the regulation of the cell biology and function of MLC1 and ClC-2 by GlialCAM. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    The Journal of Physiology 06/2015; 593(18). DOI:10.1113/JP270467 · 5.04 Impact Factor
  • Source
    • "MLC1 is homologous with carrier proteins and is confined to the plasma membrane, which indicates that it may regulate substance translocation across the cell membrane [3], [7]. Besides, it has not yet been determined whether MLC1 is localized in membrane contact regions between endothelial cells and glial cells or between different kinds of glial cells [8]–[10]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Megalencephalic leukoencephalopathy with subcortical cysts (MLC, MIM# 604004) is an autosomal recessive inherited disease mostly resulting from MLC1 mutations. In this study, we finished the functional analysis of MLC1 mutations identified recently in Chinese patients, including five newly described missense mutations (R22Q, A32V, G73E, A275T, Y278H), one known nonsense mutation (Y198X), and two known missense mutations (S69L, T118M). We found MLC1(wt) was localized to the cell periphery, whereas mutant R22Q, A32V, G73E, S69L and T118M were trapped in the lumen of endoplasmic reticulum (ER) when we transfected the wild-type and mutant MLC1 in U373MG cells. Compared to wild type, the mutant G73E, T118M, Y198X and A275T transcript decreased and all mutants except R22Q had lower protein expression in transfected U373MG cells. Therefore, we propose that all these eight MLC1 mutations had functional effect either on their protein/mRNA expression, or on their intracellular protein localization, or both.
    PLoS ONE 03/2012; 7(3):e33087. DOI:10.1371/journal.pone.0033087 · 3.23 Impact Factor
  • Source
    • "Posteriorment , en un estudi detallat del desenvolupament de ratolí , es va descriure l ' expressió de la proteïna MLC1 en tractes axonals als primers estadis de desenvolupament en el sistema nerviós central ( SNC ) , però no en la mielina en estadis posteriors ( Teijido et al . , 2007 ) . MLC1 s ' expressava en el sistema nerviós perifèric ( SNP ) , concretament en l ' epiteli sensorial , en l ' oïda interna , en la retina , en el nervi òptic i ciàtic , i en la medul·la . També es va precisar la localització de MLC1 a la membrana de contacte entre astròcits . Aquests resultats demostraven que MLC1 no formava part del"

Show more