Abstract |
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.
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Authors | E Vreugdenhil, N Datson, B Engels, J de Jong, S van Koningsbruggen, M Schaaf, E R de Kloet |
Journal | Journal of neurobiology
(J Neurobiol)
Vol. 39
Issue 1
Pg. 41-50
(Apr 1999)
ISSN: 0022-3034 [Print] United States |
PMID | 10213452
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Carrier Proteins
- DNA, Complementary
- Dcx protein, rat
- Doublecortin Domain Proteins
- Doublecortin Protein
- Microtubule-Associated Proteins
- Neuropeptides
- Phosphoproteins
- RNF34 protein, human
- Recombinant Proteins
- Calcium-Calmodulin-Dependent Protein Kinases
- Kainic Acid
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Topics |
- Amino Acid Sequence
- Animals
- Calcium-Calmodulin-Dependent Protein Kinases
(chemistry)
- Carrier Proteins
- Cloning, Molecular
- Consensus Sequence
- DNA, Complementary
- Doublecortin Domain Proteins
- Doublecortin Protein
- Gene Expression Regulation
(drug effects)
- Hippocampus
(drug effects, metabolism, pathology)
- Humans
- Kainic Acid
(toxicity)
- Male
- Microtubule-Associated Proteins
- Molecular Sequence Data
- Neuropeptides
(chemistry, genetics)
- Phosphoproteins
(biosynthesis, chemistry, genetics)
- Rats
- Rats, Wistar
- Recombinant Proteins
(biosynthesis, chemistry)
- Seizures
(chemically induced, genetics, metabolism)
- Sequence Alignment
- Sequence Homology, Amino Acid
- Transcription, Genetic
(drug effects)
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