Roles of Girdin in synaptic plasticity and memory

2014 Fiscal Year Final Research Report

• Project/Area Number: 24390095
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Nagoya University
• Principal Investigator: ASAI Naoya 名古屋大学, 医学(系)研究科(研究院), 准教授 (80273233)
• Co-Investigator(Kenkyū-buntansha): NAGAI Taku 名古屋大学, 医学部附属病院, 准教授 (10377426)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 記憶障害 / シナプス可塑性 / 蛋白リン酸化 / 疾患モデルマウス / BDNF/TekB/Akiシグナル / 海馬神経

Outline of Final Research Achievements

Girdin, an actin-binding protein involved both in the remodeling of the actin cytoskeleton and in cell migration, has been identified as a substrate of Akt at Girdin S1416. We focused on the role of Girdin S1416 phosphorylation in BDNF/TrkB/Akt signaling associated with synaptic plasticity. We found that Girdin in the hippocampus was phosphorylated at S1416 in an activity-dependent manner. Phosphorylation-deficient knock-in mice exhibited shrinkage of spines, deficit of hippocampal long-term potentiation, and memory impairment. Furthermore, Girdin interacted with Src kinase and NR2B subunit of NMDA receptor, leading to phosphorylation of the NR2B subunit and NMDA receptor activation. Our findings suggest that Girdin controls Akt-dependent NR2B phosphorylation through the interaction with Src, which is associated with synaptic plasticity in the hippocampus underlying memory formation.

Free Research Field

実験病理学