Reciprocal Activation within a Kinase-Effector Complex Underlying Persistence of Structural LTP.

ABSTRACT: Long-term synaptic plasticity requires a mechanism that converts short Ca²⁺ pulses into persistent biochemical signaling to maintain changes in the synaptic structure and function. Here, we present a novel mechanism of a positive feedback loop, formed by a reciprocally activating kinase-effector complex (RAKEC) in dendritic spines, enabling the persistence and confinement of a molecular memory. We found that stimulation of a single spine causes the rapid formation of a RAKEC consisting of CaMKII and Tiam1, a Rac-GEF. This interaction is mediated by a pseudo-autoinhibitory domain on Tiam1, which is homologous to the CaMKII autoinhibitory domain itself. Therefore, Tiam1 binding results in constitutive CaMKII activation, which in turn persistently phosphorylates Tiam1. Phosphorylat

SUBMITTER: Saneyoshi T 

PROVIDER: S-EPMC6669903 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature