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 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.
Vreugdenhil
E
E
Division of Medical Pharmacology, Leiden/Amsterdam Center for Drug Research, Leiden University, The Netherlands.
Datson
N
N
Engels
B
B
de Jong
J
J
van Koningsbruggen
S
S
Schaaf
M
M
de Kloet
E R
ER
D000595:Amino Acid Sequence; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000737:chemistry; D002352:Carrier Proteins; D003001:Cloning, Molecular; D016384:Consensus Sequence; D018076:DNA, Complementary; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007608:Kainic Acid / Q000633:toxicity*; D008297:Male; D008869:Microtubule-Associated Proteins; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000737:chemistry / Q000235:genetics; D010750:Phosphoproteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry; D012640:Seizures / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic / Q000187:drug effects*
D002352:Carrier Proteins; D018076:DNA, Complementary; C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D010750:Phosphoproteins; C461219:RNF34 protein, human; D011994:Recombinant Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D007608:Kainic Acid