Involvement of neurogranin in the modulation of calcium/calmodulin-dependent protein kinase II, synaptic plasticity, and spatial learning: A study with knockout mice
Jh. Pak et al., Involvement of neurogranin in the modulation of calcium/calmodulin-dependent protein kinase II, synaptic plasticity, and spatial learning: A study with knockout mice, P NAS US, 97(21), 2000, pp. 11232-11237
Citations number
32
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Neurogranin/RC3 is a neural-specific Ca2+-sensitive calmodulin (CaM)-bindin
g protein whose Cam-binding affinity is modulated by phosphorylation and ox
idation, Here we show that deletion of the Ng gene in mice did not result i
n obvious developmental or neuroanatomical abnormalities but caused an impa
irment of spatial learning and changes in hippocampal short- and long-term
plasticity (paired-pulse depression, synaptic fatigue, long-term potentiati
on induction). These deficits were accompanied by a decreased basal level o
f the activated Ca2+/CaM-dependent kinase II (CaMKII) (approximate to 60% o
f wild type). Furthermore, hippocampal slices of the mutant mice displayed
a reduced ability to generate activated CaMKII after stimulation of protein
phosphorylation and oxidation by treatments with okadaic acid and sodium n
itroprusside, respectively. These results indicate a central role of Ng in
the regulation of CaMKII activity with decisive influences on synaptic plas
ticity and spatial learning.