Molecular cloning and characterization of neural activity-related RING finger protein (NARF): a new member of the RBCC family is a candidate for the partner of myosin V

Activity-dependent synaptic plasticity has been thought to be a cellular ba sis of memory and learning. The late phase of longterm potentiation (L-LTP) , distinct from the early phase, lasts for up to 6 h and requires de novo s ynthesis of mRNA and protein. Many LTP-related genes are enhanced in the hi ppocampus during pentyrenetetrazol (PTZ)- and kainate (KA)-mediated neural activation: In this study, mice were administered intraperitoneal injection s of PTZ 10 times, once every 48 h, and showed an increase in seizure index es. Genes related to plasticity were efficiently induced in the mouse hippo campus. We used a PCR-based cDNA subtraction method to isolate genes that a re expressed in the hippocampus of repeatedly PTZ-treated mice. One of thes e genes, neural activity-related RING finger protein (NARF), encodes a new protein containing a RING finger, B-box zinc finger, coiled-coil (RBCC doma in) and beta -propeller (NHL) domain, and is predominantly expressed in the brain, especially in the hippocampus. In addition, KA up-regulated the exp ression of NARF mRNA in the hippocampus. This increase correlated with the activity of the NMDA receptor. By analysis using GFP-fused NARF, the protei n was found to localize in the cytoplasm. Enhanced green fluorescent protei n-fused NARF was also localized in the neurites and growth cones in neurona l differentiated P19 cells. The C-terminal beta -propeller domain of NARF i nteracts with myosin V, which is one of the most abundant myosin isoforms i n neurons. The NARF protein increases in hippocampal and cerebellar neurons after PTZ-induced seizure. These observations indicated that NARF expressi on is enhanced by seizure-related neural activities, and NARF may contribut e to the alteration of neural cellular mechanisms along with myosin V.