Seminar "Molecular Mechanisms of Hippocampal Synaptic Plasticity" by Dr. Yasunori Hayashi

Speaker:
Dr. Yasunori Hayashi, Senior team leader, Memory mechanisms, RIKEN Brain Science Institute

Title:
Molecular Mechanisms of Hippocampal Synaptic Plasticity

Abstract:
Upon induction of long-term potentiation (LTP), a cellular signaling cascade triggered by the transient Ca²⁺ influx through NMDAR leads to a persistent increase in synaptic transmission and an enlargement of the dendritic spines. There must be a mechanism within the cascade where the transient Ca²⁺ raise is converted to a persistent biochemical signaling. We propose mutually activating kinase-effector complex as a novel mechanism involved in this process. The formation of a stable heterooligomer between “T-site” of CaMKII and a RacGEF protein TIAM1, locks CaMKII in an active conformation mimicking T286 autophosphorylation, which, in turn, results in a persistent phosphorylation of TIAM1. This mutually activating complex persistently activates Rac required for the maintenance of LTP. We conclude that CaMKII, through this mutually activating mechanism, acts as a signaling hub, which, once activated by Ca²⁺, can persistently activate TIAM1 and possibly other signaling molecules in the vicinity.

Host:
Prof. Takahashi