title: A truncated Kv1.1 protein in the brain of the megencephaly mouse: expression and interaction.
abstract: BACKGROUND
  The megencephaly mouse, mceph/mceph, is epileptic and displays a dramatically increased brain volume and neuronal count. The responsible mutation was recently revealed to be an eleven base pair deletion, leading to a frame shift, in the gene encoding the potassium channel Kv1.1. The predicted MCEPH protein is truncated at amino acid 230 out of 495. Truncated proteins are usually not expressed since nonsense mRNAs are most often degraded. However, high Kv1.1 mRNA levels in mceph/mceph brain indicated that it escaped this control mechanism. Therefore, we hypothesized that the truncated Kv1.1 would be expressed and dysregulate other Kv1 subunits in the mceph/mceph mice.
  
  
  RESULTS
  We found that the MCEPH protein is expressed in the brain of mceph/mceph mice. MCEPH was found to lack mature (Golgi) glycosylation, but to be core glycosylated and trapped in the endoplasmic reticulum (ER). Interactions between MCEPH and other Kv1 subunits were studied in cell culture, Xenopus oocytes and the brain. MCEPH can form tetramers with Kv1.1 in cell culture and has a dominant negative effect on Kv1.2 and Kv1.3 currents in oocytes. However, it does not retain Kv1.2 in the ER of neurons.
  
  
  CONCLUSIONS
  The megencephaly mice express a truncated Kv1.1 in the brain, and constitute a unique tool to study Kv1.1 trafficking relevant for understanding epilepsy, ataxia and pathologic brain overgrowth.
authors.affiliation: Department of Molecular Medicine and Surgery, CMM, Karolinska Hospital, Karolinska Institutet, 171 76 Stockholm, Sweden. ann-sophie.persson@cmm.ki.se
authors.forename: Ann-Sophie
authors.initials: AS
authors.lastname: Persson
authors.forename: Göran
authors.initials: G
authors.lastname: Klement
authors.forename: Malin
authors.initials: M
authors.lastname: Almgren
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Sahlholm
authors.forename: Johanna
authors.initials: J
authors.lastname: Nilsson
authors.forename: Susanna
authors.initials: S
authors.lastname: Petersson
authors.forename: Peter
authors.initials: P
authors.lastname: Arhem
authors.forename: Martin
authors.initials: M
authors.lastname: Schalling
authors.forename: Catharina
authors.initials: C
authors.lastname: Lavebratt
mesh_terms: D000818:Animals; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000002:abnormalities* / Q000473:pathology; D002460:Cell Line; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D016368:Frameshift Mutation; D005786:Gene Expression Regulation / Q000235:genetics*; D006031:Glycosylation; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D047468:Immunoprecipitation / Q000379:methods; D051662:Kv1.1 Potassium Channel / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D051663:Kv1.2 Potassium Channel / Q000378:metabolism; D008564:Membrane Potentials / Q000235:genetics / Q000502:physiology / Q000528:radiation effects; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009865:Oocytes / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000235:genetics; D021381:Protein Transport / Q000235:genetics; D014162:Transfection / Q000379:methods; D014981:Xenopus
chemical_list: D051663:Kv1.2 Potassium Channel; D010446:Peptide Fragments; D051662:Kv1.1 Potassium Channel