title: Motor discoordination in mutant mice lacking junctophilin type 3.
abstract: Junctional complexes between the plasma membrane and endoplasmic reticulum (ER), often called "subsurface cisternae" or "peripheral coupling," are shared by excitable cells. These junctional membranes probably provide structural foundation for functional crosstalk between cell-surface and intracellular ionic channels. Our current studies have indicated that junctophilins (JPs) take part in the formation of junctional membrane complexes by spanning the ER membrane and interacting with the plasma membrane. Of the JP subtypes defined, JP type 3 (JP-3) is specifically expressed in neurons in the brain. It has been currently reported that triplet repeat expansions in the JP-3 gene are associated with Huntington's disease-like symptoms including motor disorder in human. To survey the physiological role of JP-3, we generated the knockout mice. The JP-3-knockout mice grew and reproduced normally, and we did not observe any morphological abnormality in the mutant brain. In the behavioral study, the mutant mice showed impaired performance specifically in balance/motor coordination tasks. Although obvious defects could not be observed in excitatory transmission among cerebellar neurons from the mutant mice, the data indicate that JP-3 plays an active role in certain neurons involved in motor coordination.
authors.affiliation: Department of Biochemistry, Graduate School of Medicine, Tohoku University, CREST, Japan Science and Technology Corporation, Seiryo-machi, Sendai, Miyagi.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Nishi
authors.forename: Kouichi
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Koji
authors.initials: K
authors.lastname: Kuriyama
authors.forename: Shinji
authors.initials: S
authors.lastname: Komazaki
authors.forename: Masanobu
authors.initials: M
authors.lastname: Kano
authors.forename: Shigenobu
authors.initials: S
authors.lastname: Shibata
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takeshima
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism; D002462:Cell Membrane / Q000648:ultrastructure; D002478:Cells, Cultured; D002531:Cerebellum / Q000002:abnormalities; D004721:Endoplasmic Reticulum / Q000648:ultrastructure; D007700:Kinetics; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009048:Motor Skills; D019957:Motor Skills Disorders / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D011689:Purkinje Cells / Q000502:physiology / Q000648:ultrastructure; D009435:Synaptic Transmission; D014018:Tissue Distribution
chemical_list: D008565:Membrane Proteins; C412507:junctophilin