1SEP-04 Activity-dependent gene expression in learning and memory(1SEP Cooperativity in shaping the nerve cell function,Symposium,The 52nd Annual Meeting of the Biophysical Society of Japan(BSJ2014))

Abstract

Ca 2+ /Calmodulin-dependent kinase II (CaMKII) is one of the most important signaling molecules for synaptic plasticity underlying learning and memory. Here, we developed a photo-activatable CaMKII (paCaMKII). Light-induced spine specific CaMKII activation successfully induced the structural plasticity, which suggesting that CaMKII activation is sufficient for the plasticity. In addition, we imaged the activity of Rho GTPases, RhoA and Cdc42, by using 2pFLIM and found that these molecules are activated via CaMKII. Furthermore, since the loss of function assay suggests that RhoA and Cdc42 works for triggering and maintaining the structural plasticity, respectively, these molecules may cooperatively work for establishing the spine structural plasticity. The plasma membrane (PM) of neuronal cells is split into two regions with distinct functions, the somatodendritic domain (neuronal signal input) and axon (output). Many PM molecules reside in either one of the two domains, which is enabled by the presence of a diffusion barrier in the PM in the initial segment (IS) region, the interface between the two domains. The diffusion barrier is formed by the cooperative assembly and binding of transmembrane proteins and scaffolding actin-binding molecules. Recently, we found that the diffusion barrier is a molecule-selective filter, allowing GPI-anchored proteins to pass through, but not transmembrane proteins and phospholipids. The mechanism for the selective passage is becoming clear, which will be discussed in this talk. Long-term memory formation requires a complex coordination of signaling to enable specific storage of otherwise transient information acquired as memory events happen. How does such conversion from labile into a more stable information occur? We here our recent on multiple levels of signal cooperation, at the synaptic, dendritic and nuclear compartments of a neuron, which together contribute to achieving this formidable signal processing. Recent human genome sequencing studies indicate that maladaptation of such signaling cascades may underlie several forms of