Kainate-elicited seizures induce mRNA encoding a CaMK-related peptide: a putative modulator of kinase activity in rat hippocampus

Publication Type:

Journal Article


J Neurobiol, Volume 39, Number 1, p.41-50 (1999)


0022-3034 (Print)0022-30

DOI Name (links to online publication)



Amino Acid Sequence; Animals; Calcium-Calmodulin-Dependent Protein Kinases/chemistry; Cloning; Molecular; Consensus Sequence; DNA; Complementary; Gene Expression Regulation/drug effects; Hippocampus/drug effects/*metabolism/pathology; Humans; Kainic Acid/


By means of differential display techniques, we have previously identified an mRNA transcript whose expression is highly induced in the rat hippocampus by kainate-elicited seizures. Here, we report the cloning of a corresponding cDNA encoding a 55-amino-acid, serine-rich peptide which contains four predicted phosphorylation sites. The peptide was designated CaMK-related peptide (CARP) as it shares significant amino acid sequence identity with part of a novel putative calcium/calmodulin-dependent kinase (CaMK-VI) that was also cloned in this study. It appears that CARP and CaMK-VI are derived from the same gene through differential splicing. Intriguingly, CARP also exhibits 64% amino acid sequence identity with the C-terminal part of human doublecortin, encoded by a recently identified gene which is mutated in patients with X-linked lissencephaly and the double-cortex syndrome. In addition, the structure of CARP resembles the autoinhibitory, serine-rich N-terminal domain of CaMK-IV, suggesting a possible modulatory role of CARP with respect to CaMK activity. Northern blot analysis and in situ hybridization experiments showed that CARP mRNA is specifically induced by kainate-elicited seizures in the dentate gyrus and in the pyramidal layers CA1 and CA2, but not in CA3. In contrast, kainate-induced seizures did not change the level of expression of the CaMK-VI gene. We propose that CARP induction leads to the modulation of kinase activity in specific subregions of the rat hippocampus, providing a negative feedback mechanism for seizure-induced kinases.