Biomedical subjects

Elod Kortvely

Publications and source records attributed to Elod Kortvely.

5 recordsLinked to original sources

PubMed2005

Cloning and characterization of rat importin 9: implication for its neuronal function.

We describe the structure of the rat importin 9 gene, together with its transcripts and the encoded protein with its putative functional domains. The importin 9 gene contains 24 exons in a genomic region spanning >52,000 bp. It is transcribed into two mRNAs, generated by means of alternative polyadenylation site usage arranged in tandem. Both transcripts possess the same noncanonical polyadenylation signal (AGUAAA) in rat, this hexamer being conserved in all vertebrates examined. Additionally, intron 8 is bordered by AT-AC dinucleotides. Importin 9 is expressed throughout adult rat tissues, but the 114-kDa Importin 9 protein was detected only in the brain. The localization of the Importin 9 protein was examined by immunohistochemistry in both adult rat tissues and primary hippocampal cell cultures. The strongest labeling was detected in vivo in areas populated by neurons in high density and also in the dendritic processes emanating from these cells. This protein was clearly concentrated in the nuclei of these cells, although their cytoplasms too were heavily labeled. Strong cytoplasmic and very strong nuclear staining was found in a vast majority of the cells with neuronal morphology in vitro. Cultured cells with glial morphology generally exhibited a weaker cytoplasmic labeling. In these cells, the signal decorated the nuclear envelope without nuclear staining and gradually dwindled toward the cell periphery. These results hint at the cell- or tissue-type specific functions of this type of importin protein.

Amino Acid Sequence↗

PubMed2005

Multiple calmodulin mRNAs are selectively transported to functionally different neuronal and glial compartments in the rat hippocampus. An electron microscopic in situ hybridization study.

The ultrastructural distribution of the calmodulin (CaM) mRNAs transcribed from the three CaM genes was studied in the CA1 region of the adult rat hippocampus by means of electron microscopic in situ hybridization. Digoxigenin-labeled CaM gene-specific riboprobes were detected with nanogold-anti-digoxigenin antibody conjugate. The CaM mRNAs were differentially distributed in both the neuronal and glial cell compartments. The greatest difference in neuronal distribution of the CaM mRNAs was found in the dendrites, where the mRNAs transcribed from the CaM I and III genes were much more abundant than the CaM II mRNA. The neuronal perikarya were heavy labeled for all the CaM mRNAs. Interestingly, the myelinated axons and axon terminals also contained small amounts of nanogold particles for all the CaM mRNAs, which diminished with increasing distance from the soma. Most of the synaptic profiles, however, contained labeling only in the postsynaptic region. The CaM mRNAs were differentially distributed in the glial cells. While the glial cell somata were only lightly labeled, surprisingly concentrated labeling was present in the perisynaptic and perivascular astrocytic processes. In general, the CaM II mRNA was the least represented in the glial processes. Only a very low CaM gene expression was observed in the endothelial and resting microglial cells. These results provide ultrastructural evidence for differential targeting of the multiple CaM mRNA transcripts to the intracellular compartments and suggest their microdomain-specific regulation.

Animals↗

PubMed2004

Calmodulin, and various ways to regulate its activity.

Calmodulin (CaM), the ubiquitous calcium sensor protein, is involved in almost all intracellular events. In higher vertebrates, a single protein is encoded by multiple, co-expressed genes, and the number of discrete CaM transcripts produced by a single cell is further increased by intense alternative polyadenylation signal usage. It appears most likely that the individual transcripts possess unique intracellular fates, so that this apparent redundancy multiplies the number of challenges which the cell is able to respond to. The promoter regions of the different CaM genes have been analyzed. Several putative transcription factor binding sites have been identified; however, the elements responsible for their generally strong co-expression, and even those providing different spatial and temporal control, remain to be elucidated. Moreover, a powerful posttranscriptional control mechanism is responsible for the establishment of local intracellular CaM mRNA pools. This is mainly achieved by the selective targeting of mRNAs to various cellular domains, although regulation via mRNA stability cannot be ruled out. Finally, tailoring of the CaM protein itself offers the fastest way whereby the properties of this Ca2+-receptor protein can be changed. Indeed, several posttranslational modifications of CaM were described earlier, but their functions are not yet understood. Here, we briefly review the regulatory levels from the gene transcription to the covalent modifications of the synthesized protein.

Binding Sites↗

PubMed2003

Intracellular targeting of calmodulin mRNAs in primary hippocampal cells.

We investigated the intracellular distribution of the mRNAs corresponding to the three non-allelic CaM genes in cultured hippocampal cells by in situ hybridization with digoxigenin-labeled gene-specific riboprobes. In neurons the perikaryon was heavily stained and strong dendritic mRNA targeting was detected for all three CaM genes. The color labeling exhibited a punctate distribution, suggesting that CaM mRNAs are transported in RNA granules. Immunocytochemistry for S100 demonstrated that glial cells express CaM mRNAs at a very low level. A minority of the cultured cells were negative for either labeling.

Animals↗

PubMed2002

Differential calmodulin gene expression in the rodent brain.

Apparently redundant members of the calmodulin (CaM) gene family encode for the same amino acid sequence. CaM, a ubiquitous cytoplasmic calcium ion receptor, regulates the function of a variety of target molecules even in a single cell. Maintenance of the fidelity of the active CaM-target interactions in different compartments of the cell requires a rather complex control of the total cellular CaM pool comprising multiple levels of regulatory circuits. Among these mechanisms, it has long been proposed that a multigene family maximizes the regulatory potentials at the level of the gene expression. CaM genes are expressed at a particularly profound level in the mammalian central nervous system (CNS), especially in the highly polarized neurons. Thus, in the search for clear evidence of the suggested differential expression of the CaM genes, much of the research has been focused on the elements of the CNS. This review aims to give a comprehensive survey on the current understanding of this field at the level of the regulation of CaM mRNA transcription and distribution in the rodent brain. The results indicate that the CaM genes are indeed expressed in a gene-specific manner in the developing and adult brain under physiological conditions. To establish local CaM pools in distant intracellular compartments (dendrites and glial processes), local protein synthesis from differentially targeted mRNAs is also employed. Moreover, the CaM genes are controlled in a unique, gene-specific fashion when responding to certain external stimuli. Additionally, putative regulatory elements have been identified on the CaM genes and mRNAs.

Animals↗