Disturbance of cerebellar synaptic maturation in mutant mice lacking BSRPs, a novel brain-specific receptor-like protein family.
By DNA cloning, we have identified the BSRP (brain-specific receptor-like proteins) family of three members in mammalian genomes. BSRPs were predominantly expressed in the soma and dendrites of neurons and localized in the endoplasmic reticulum (ER). Expression levels of BSRPs seemed to fluctuate greatly during postnatal cerebellar maturation. Triple-knockout mice lacking BSRP members exhibited motor discoordination, and Purkinje cells (PCs) were often innervated by multiple climbing fibers with different neuronal origins in the mutant cerebellum. Moreover, the phosphorylation levels of protein kinase Calpha (PKCalpha) were significantly downregulated in the mutant cerebellum. Because cerebellar maturation and plasticity require metabotropic glutamate receptor signaling and resulting PKC activation, BSRPs are likely involved in ER functions supporting PKCalpha activation in PCs.
Miyazaki
Taisuke
T
Department of Anatomy, Hokkaido University, School of Medicine, Sapporo, Japan.
Hashimoto
Kouichi
K
Uda
Atsushi
A
Sakagami
Hiroyuki
H
Nakamura
Yoshitaka
Y
Saito
Shin-ya
SY
Nishi
Miyuki
M
Kume
Hideaki
H
Tohgo
Akira
A
Kaneko
Izumi
I
Kondo
Hisatake
H
Fukunaga
Kohji
K
Kano
Masanobu
M
Watanabe
Masahiko
M
Takeshima
Hiroshi
H
D000818:Animals; D002531:Cerebellum / Q000166:cytology / Q000254:growth & development*; D003712:Dendrites / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D004789:Enzyme Activation / Q000235:genetics; D016678:Genome / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D005810:Multigene Family / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000378:metabolism*; D010766:Phosphorylation; D051571:Protein Kinase C-alpha / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000235:genetics; D011597:Psychomotor Performance / Q000502:physiology; D011689:Purkinje Cells / Q000166:cytology / Q000502:physiology*; D017470:Receptors, Glutamate / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013569:Synapses / Q000378:metabolism*
D009419:Nerve Tissue Proteins; D017470:Receptors, Glutamate; D051571:Protein Kinase C-alpha