Role of SPAL-1 in Higher Brain Function and Molecular Mechanism of Psychiatric Disorders

2016 Fiscal Year Final Research Report

• Project/Area Number: 26460385
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Okinawa Institute of Science and Technology Graduate University (2016); The University of Tokyo (2014-2015)
• Principal Investigator: Matsuura Ken 沖縄科学技術大学院大学, 細胞シグナルユニット, スタッフサイエンティスト (10625742)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 神経科学

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.

Free Research Field

分子生物学