title: 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.affiliation: Department of Pediatrics/Child Neurology, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands. ms.vanderknaap@vumc.nl
authors.forename: Ilja
authors.initials: I
authors.lastname: Boor
authors.forename: Machiel
authors.initials: M
authors.lastname: Nagtegaal
authors.forename: Wouter
authors.initials: W
authors.lastname: Kamphorst
authors.forename: Paul
authors.initials: P
authors.lastname: van der Valk
authors.forename: Jan C
authors.initials: JC
authors.lastname: Pronk
authors.forename: Jack
authors.initials: J
authors.lastname: van Horssen
authors.forename: Argirios
authors.initials: A
authors.lastname: Dinopoulos
authors.forename: Kevin E
authors.initials: KE
authors.lastname: Bove
authors.forename: Ignacio
authors.initials: I
authors.lastname: Pascual-Castroviejo
authors.forename: Francesco
authors.initials: F
authors.lastname: Muntoni
authors.forename: Raúl
authors.initials: R
authors.lastname: Estévez
authors.forename: Gert C
authors.initials: GC
authors.lastname: Scheper
authors.forename: Marjo S
authors.initials: MS
authors.lastname: van der Knaap
mesh_terms: D051401:Aquaporin 4 / Q000378:metabolism; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D001932:Brain Neoplasms / Q000378:metabolism; D020863:Central Nervous System Cysts / Q000378:metabolism* / Q000473:pathology; D049028:Dystrophin-Associated Protein Complex / Q000378:metabolism*; D005910:Glioma / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D020271:Heredodegenerative Disorders, Nervous System / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D008565:Membrane Proteins / Q000378:metabolism*; D009103:Multiple Sclerosis / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D000098854:Kcnj10 Channel
chemical_list: C496030:AQP4 protein, human; D051401:Aquaporin 4; D049028:Dystrophin-Associated Protein Complex; D006023:Glycoproteins; D000098854:Kcnj10 Channel; C425069:MLC1 protein, human; D008565:Membrane Proteins; D024661:Potassium Channels, Inwardly Rectifying