MLC1 is associated with the dystrophin-glycoprotein complex at astrocytic endfeet

Ilja Boor, Machiel Nagtegaal, Wouter Kamphorst, Paul van der Valk, Jan C Pronk, Jack van Horssen, Argirios Dinopoulos, Kevin E Bove, Ignacio Pascual-Castroviejo, Francesco Muntoni, Raúl Estévez, Gert C Scheper, Marjo S van der Knaap

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Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a progressive cerebral white matter disease with onset in childhood, caused by mutations in the MLC1 gene. MLC1 is a protein with unknown function that is mainly expressed in the brain in astrocytic endfeet at the blood-brain and cerebrospinal fluid-brain barriers. It shares its localization at astrocytic endfeet with the dystrophin-associated glycoprotein complex (DGC). The objective of the present study was to investigate the possible association of MLC1 with the DGC. To test this hypothesis, (co)-localization of DGC-proteins and MLC1 was analyzed by immunohistochemical stainings in gliotic brain tissue from a patient with multiple sclerosis, in glioblastoma tissue and in brain tissue from an MLC patient. In control tissue, a direct protein interaction was tested by immunoprecipitation. Results revealed that MLC1 is co-localized with DGC-proteins in gliotic brain tissue. We demonstrated that both MLC1 and aquaporin-4, a member of the DGC, were redistributed in glioblastoma cells. In MLC brain tissue, we showed absence of MLC1 and altered expression of several DGC-proteins. We demonstrated a direct protein interaction between MLC1 and Kir4.1. From these results we conclude that MLC1 is associated with the DGC at astrocytic endfeet.

Original languageEnglish
Pages (from-to)403-10
Number of pages8
JournalActa Neuropathologica
Issue number4
Publication statusPublished - Oct 2007


  • Aquaporin 4/metabolism
  • Astrocytes/metabolism
  • Blotting, Western
  • Brain Neoplasms/metabolism
  • Brain/metabolism
  • Central Nervous System Cysts/metabolism
  • Dystrophin-Associated Protein Complex/metabolism
  • Glioma/metabolism
  • Glycoproteins/metabolism
  • Heredodegenerative Disorders, Nervous System/metabolism
  • Humans
  • Immunohistochemistry
  • Immunoprecipitation
  • Membrane Proteins/metabolism
  • Multiple Sclerosis/metabolism
  • Potassium Channels, Inwardly Rectifying/metabolism

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