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 basis of memory and learning. The late phase of long-term potentiation (L-LTP), distinct from the early phase, lasts for up to 6 h and requires de novo synthesis of mRNA and protein. Many LTP-related genes are enhanced in the hippocampus during pentyrenetetrazol (PTZ)- and kainate (KA)-mediated neural activation. In this study, mice were administered intraperitoneal injections of PTZ 10 times, once every 48 h, and showed an increase in seizure indexes. Genes related to plasticity were efficiently induced in the mouse hippocampus. We used a PCR-based cDNA subtraction method to isolate genes that are expressed in the hippocampus of repeatedly PTZ-treated mice. One of these genes, neural activity-related RING finger protein (NARF), encodes a new protein containing a RING finger, B-box zinc finger, coiled-coil (RBCC domain) and beta-propeller (NHL) domain, and is predominantly expressed in the brain, especially in the hippocampus. In addition, KA up-regulated the expression of NARF mRNA in the hippocampus. This increase correlated with the activity of the NMDA receptor. By analysis using GFP-fused NARF, the protein was found to localize in the cytoplasm. Enhanced green fluorescent protein-fused NARF was also localized in the neurites and growth cones in neuronal differentiated P19 cells. The C-terminal beta-propeller domain of NARF interacts with myosin V, which is one of the most abundant myosin isoforms in neurons. The NARF protein increases in hippocampal and cerebellar neurons after PTZ-induced seizure. These observations indicated that NARF expression is enhanced by seizure-related neural activities, and NARF may contribute to the alteration of neural cellular mechanisms along with myosin V.
Ohkawa
N
N
Department of Biology, Faculty of Science, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan. nokawa@bio.s.chiba-u.ac.jp
Kokura
K
K
Matsu-Ura
T
T
Obinata
T
T
Konishi
Y
Y
Tamura
T A
TA
D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D019677:Artificial Gene Fusion; D002454:Cell Differentiation; D002460:Cell Line; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism; D003001:Cloning, Molecular; D003292:Convulsants / Q000494:pharmacology; D018076:DNA, Complementary / Q000235:genetics; D049452:Green Fluorescent Proteins; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism / Q000503:physiopathology; D007425:Intracellular Membranes / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D009218:Myosins / Q000502:physiology; D020932:Nerve Growth Factor / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000502:physiology*; D010433:Pentylenetetrazole / Q000494:pharmacology; D011506:Proteins; D012333:RNA, Messenger / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology; D014018:Tissue Distribution; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases
D003292:Convulsants; D018076:DNA, Complementary; D008164:Luminescent Proteins; D009687:Nuclear Proteins; D011506:Proteins; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D000070584:Tripartite Motif Proteins; D049452:Green Fluorescent Proteins; D020932:Nerve Growth Factor; C485687:Trim2 protein, mouse; D044767:Ubiquitin-Protein Ligases; D009218:Myosins; D010433:Pentylenetetrazole