Arc, a growth factor and activity-regulated gene, encodes a novel cytoskeleton-associated protein that is enriched in neuronal dendrites.
Neuronal activity is an essential stimulus for induction of plasticity and normal development of the CNS. We have used differential cloning techniques to identify a novel immediate-early gene (IEG) cDNA that is rapidly induced in neurons by activity in models of adult and developmental plasticity. Both the mRNA and the encoded protein are enriched in neuronal dendrites. Analysis of the deduced amino acid sequence indicates a region of homology with alpha-spectrin, and the full-length protein, prepared by in vitro transcription/translation, coprecipitates with F-actin. Confocal microscopy of the native protein in hippocampal neurons demonstrates that the IEG-encoded protein is enriched in the subplasmalemmal cortex of the cell body and dendrites and thus colocalizes with the actin cytoskeletal matrix. Accordingly, we have termed the gene and encoded protein Arc (activity-regulated cytoskeleton-associated protein). Our observations suggest that Arc may play a role in activity-dependent plasticity of dendrites.
Lyford
G L
GL
Department of Neuroscience, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Yamagata
K
K
Kaufmann
W E
WE
Barnes
C A
CA
Sanders
L K
LK
Copeland
N G
NG
Gilbert
D J
DJ
Jenkins
N A
NA
Lanahan
A A
AA
Worley
P F
PF
D000199:Actins / Q000302:isolation & purification / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism* / Q000502:physiology; D002645:Chickens; D003598:Cytoskeletal Proteins / Q000096:biosynthesis* / Q000235:genetics*; D003599:Cytoskeleton / Q000378:metabolism*; D018076:DNA, Complementary; D003712:Dendrites / Q000378:metabolism*; D005786:Gene Expression Regulation; D015723:Gene Library; D017781:Genes, Immediate-Early; D006624:Hippocampus / Q000378:metabolism; D017403:In Situ Hybridization; D008297:Male; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics*; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism*; D014176:Protein Biosynthesis; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D017386:Sequence Homology, Amino Acid; D013049:Spectrin / Q000235:genetics; D014158:Transcription, Genetic
D000199:Actins; D003598:Cytoskeletal Proteins; D018076:DNA, Complementary; D009419:Nerve Tissue Proteins; C092069:activity regulated cytoskeletal-associated protein; D013049:Spectrin