Motor discoordination in mutant mice lacking junctophilin type 3.
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.
Nishi
Miyuki
M
Department of Biochemistry, Graduate School of Medicine, Tohoku University, CREST, Japan Science and Technology Corporation, Seiryo-machi, Sendai, Miyagi.
Hashimoto
Kouichi
K
Kuriyama
Koji
K
Komazaki
Shinji
S
Kano
Masanobu
M
Shibata
Shigenobu
S
Takeshima
Hiroshi
H
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
D008565:Membrane Proteins; C412507:junctophilin