Disturbance of cerebellar synaptic maturation in mutant mice lacking BSRPs, a novel brain-specific receptor-like protein family

• Published in: FEBS letters Vol. 580; no. 17; pp. 4057 - 4064
• Main Authors: Miyazaki, Taisuke, Hashimoto, Kouichi, Uda, Atsushi, Sakagami, Hiroyuki, Nakamura, Yoshitaka, Saito, Shin-ya, Nishi, Miyuki, Kume, Hideaki, Tohgo, Akira, Kaneko, Izumi, Kondo, Hisatake, Fukunaga, Kohji, Kano, Masanobu, Watanabe, Masahiko, Takeshima, Hiroshi
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 24-07-2006
• Subjects: Animals; Ca2+/calmodulin-dependent protein kinase II; CaMKII; cAMP-dependent protein kinase; Cerebellum; Cerebellum - cytology; Cerebellum - growth & development; climbing fiber; Dendrites - metabolism; Down-Regulation - genetics; Endoplasmic reticulum; Enzyme Activation - genetics; EPSC; ERK; excitatory postsynaptic current; extracellular signal-regulated kinase; Genome - physiology; inositol 1,4,5-trisphosphate receptor type 1; IP3R1; Knockout mouse; metabotropic glutamate receptor subtype 1; mGluR1; Mice; Mice, Knockout; Mice, Neurologic Mutants; Multigene Family - physiology; Nerve Tissue Proteins - deficiency; Nerve Tissue Proteins - metabolism; parallel fiber; Phosphorylation; PKA; PKC; Protein kinase C; Protein Kinase C-alpha - metabolism; Protein Processing, Post-Translational - genetics; Psychomotor Performance - physiology; Purkinje cell; Purkinje Cells - cytology; Purkinje Cells - physiology; Receptors, Glutamate - metabolism; Signal Transduction - physiology; Synapses - metabolism; TKO mice; triple-knockout mice lacking BSRP members; vesicular glutamate transporter; VGluT; Cerebellum; IP3R1; Protein kinase C; CF; PKA; VGluT; PKC; ER; CaMKII; PC; PF; Knockout mouse; mGluR1; EPSC; TKO mice; Endoplasmic reticulum; ERK
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2006.06.043

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 Cα (PKCα) 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 PKCα activation in PCs.