Narp and NP1 form heterocomplexes that function in developmental and activity-dependent synaptic plasticity.
Narp is a neuronal immediate early gene that plays a role in excitatory synaptogenesis. Here, we report that native Narp in brain is part of a pentraxin complex that includes NP1. These proteins are covalently linked by disulfide bonds into highly organized complexes, and their relative ratio in the complex is dynamically dependent upon the neuron's activity history and developmental stage. Complex formation is dependent on their distinct N-terminal coiled-coil domains, while their closely homologous C-terminal pentraxin domains mediate association with AMPA-type glutamate receptors. Narp is substantially more effective in assays of cell surface cluster formation, coclustering of AMPA receptors, and excitatory synaptogenesis, yet their combined expression results in supraadditive effects. These studies support a model in which Narp can regulate the latent synaptogenic activity of NP1 by forming mixed pentraxin assemblies. This mechanism appears to contribute to both activity-independent and activity-dependent excitatory synaptogenesis.
Xu
Desheng
D
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Hopf
Carsten
C
Reddy
Radhika
R
Cho
Richard W
RW
Guo
Liping
L
Lanahan
Anthony
A
Petralia
Ronald S
RS
Wenthold
Robert J
RJ
O'Brien
Richard J
RJ
Worley
Paul
P
D000595:Amino Acid Sequence; D000818:Animals; D002097:C-Reactive Protein / Q000096:biosynthesis / Q000737:chemistry* / Q000502:physiology* / Q000648:ultrastructure; D019556:COS Cells; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000502:physiology* / Q000648:ultrastructure; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000502:physiology* / Q000648:ultrastructure; D006801:Humans; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000737:chemistry* / Q000502:physiology* / Q000648:ultrastructure; D009473:Neuronal Plasticity / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017386:Sequence Homology, Amino Acid; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure; D000099153:Pentraxins
D002097:C-Reactive Protein; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; D009419:Nerve Tissue Proteins; D000099153:Pentraxins; C081466:narP protein, E coli