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


Brain Science Institute, RIKEN, Wako, Saitama 351-0198, Japan; Department of Pharmacology, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan. Electronic address: [Email]


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. Phosphorylated Tiam1 promotes stable actin-polymerization through Rac1, thereby maintaining the structure of the spine during LTP. The RAKEC can store biochemical information in small subcellular compartments, thus potentially serving as a general mechanism for prolonged and compartmentalized signaling.


Ca(2+)/calmodulin-dependent protein kinase II,Rho family small GTPase,actin cytoskeleton,dendritic spine,guanine-nucleotide exchange factor,long-term potentiation,pseudo-autoinhibitory domain,reciprocally activating kinase-effector complex (RAKEC),synaptic plasticity,

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