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

By means of differential display techniques, we have previously identified an mRNA transcript whose expression is highly induced in the rat hippocampu s by kainate-elicited seizures. Here, we report the cloning of a correspond ing cDNA encoding a 55-amino-acid, serine-rich peptide which contains four predicted phosphorylation sites. The peptide was designated CaMK-related pe ptide (CARP) as it shares significant amino acid sequence identity with par t of a novel putative calcium/calmodulin-dependent kinase (CaMK-VI) that wa s also cloned in this study. It appears that CARP and CaMK-VI are derived f rom the same gene through differential splicing. Intriguingly, CARP also ex hibits 64% amino acid sequence identity with the C-terminal part of human d oublecortin, encoded by a recently identified gene which is mutated in pati ents with X-linked lissencephaly and the double-cortex syndrome. In additio n, the structure of CARP resembles the autoinhibitory, serine-rich N-termin al domain of CaMK-IV, suggesting a possible modulatory role of CARP with re spect to CaMK activity. Northern blot analysis and in situ hybridization ex periments 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 hippoc ampus, providing a negative feedback mechanism for seizure-induced kinases. (C) 1999 John Wiley & Sons, Inc.