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

Abstract

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.

• Authors: 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
• Journal: Acta neuropathologica (Acta Neuropathol) Vol. 114 Issue 4 Pg. 403-10 (Oct 2007) ISSN: 0001-6322 [Print] Germany
• PMID: 17628813 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• AQP4 protein, human
• Aquaporin 4
• Dystrophin-Associated Protein Complex
• Glycoproteins
• Kcnj10 (channel)
• MLC1 protein, human
• Membrane Proteins
• Potassium Channels, Inwardly Rectifying

Topics

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