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Journal of Neuroscience, Vol 16, 2463-2478, Copyright © 1996 by Society for Neuroscience
Narp, a novel member of the pentraxin family, promotes neurite outgrowth and is dynamically regulated by neuronal activity
CC Tsui, NG Copeland, DJ Gilbert, NA Jenkins, C Barnes and PF Worley
Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Stimulus-linked RNA and protein synthesis is required for establishment of
long-term neuroplasticity. To identify molecular mechanisms underlying
long-term neuroplasticity, we have used differential cDNA techniques to
clone a novel immediate-early gene (IEG) that is rapidly induced in neurons
of the hippocampus and cortex by physiological synaptic activity. Analysis
of the deduced amino acid sequence indicates homology to members of the
pentraxin family of secreted lectins that include C-reactive protein and
serum amyloid P component. Regions of homology include an 8 amino acid
"pentraxin signature" sequence and a characteristic pentraxin
calcium-binding domain. We have termed this gene and the encoded protein
Narp (from neuronal activity- regulated pentraxin). Biochemical analyses
confirm the presence of a functional signal sequence, and Narp is secreted
by transfected COS-1 cells in culture. Additionally, Narp binds to agar
matrix in a calcium- dependent manner consistent with the lectin properties
of the pentraxin family. When cocultured with Narp-secreting COS-1 cells,
neurons of cortical explants exhibit enhanced growth of neuronal dendritic
processes. Neurite outgrowth-promoting activity is also observed using
partially purified Narp and can be specifically immunodepleted,
demonstrating that Narp is the active principle. Narp is fully active at a
concentration of approximately 40 ng/ml, indicating a potency similar to
known peptide growth factors. Because Narp is rapidly regulated by neuronal
activity, its lectin and growth-promoting activities are likely to play
role in the modification of cellular properties that underlie long-term
plasticity.
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