| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
|---|
| Outline of Final Research Achievements |
SPAL-1 has been proposed to play critical roles in synaptic function in cultured neurons. However, physiological role of SPAL-1 in vivo remains unknown. To tackle this issue, we generated SPAL-1 KO mice. SPAL-1 KO mice showed hyperactivity, learning impairments and autistic-like social behaviour. In search of a clue for molecular role of SPAL-1 in the brain, we performed a rigorous proteomic screen for native complex of SPAL-1 in mouse forebrain and identified the Neurabin family of proteins, which are known for their involvement in GPCR regulation. Subsequent phenotypic analyses revealed that Spal-1 KO mice show opposite phenotypes of Neurabin1 KO and Neurabin2 KO mice in epileptic seizure susceptibility and reduced or enhanced sedative response to agonist stimulations in the GPCR pathway dependent manner. Our results uncover critical roles of SPAL-1 in the higher brain function and may provide novel insight into Neurabin mediated regulation of GPCR signaling.
|
