Bart Engels - Academia.edu (original) (raw)

Papers by Bart Engels

Brain research. Molecular brain research, Jan 5, 2004

Recently, we have cloned two splice variants of the doublecortin-like kinase (DCLK) gene, called ... more Recently, we have cloned two splice variants of the doublecortin-like kinase (DCLK) gene, called DCLK-short-A and -B, both of which encode calcium/calmodulin-dependent protein kinase (CaMK)-like proteins with different C-terminal ends. Using in situ hybridization, we have found that both are highly expressed in limbic structures of the brain and that their expression differs in a number of brain areas. DCLK-short-A is relatively more strongly expressed than DCLK-short-B in the subependymal zone. The DCLK-short-B variant shows stronger expression in the cortex, the ventromedial and dorsomedial hypothalamic nuclei, the arcuate nucleus, the zona incerta and the subincertal nucleus. Also, within the hippocampus, the relative distribution of these two splice variants differs. DCLK-short-B expression compared to DCLK-short-A is highest in the CA1 area. The expression of the A variant is highest in the CA3/CA4 area. Additionally, DCLK-short-B is expressed at a higher level than DCLK-short-...

Journal of Experimental Biology, 2004

PLoS ONE, 2012

MiRNAs can regulate gene expression through versatile mechanisms that result in increased or decr... more MiRNAs can regulate gene expression through versatile mechanisms that result in increased or decreased expression of the targeted mRNA and it could effect the expression of thousands of protein in a particular cell. An increasing body of evidence suggest that miRNAs action can be modulated by proteins that bind to the same 3&amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;UTRs that are targeted by miRNAs, suggesting that other factors apart from miRNAs and their target sites determine miRNA-modulation of gene expression. We applied an affinity purification protocol using biotinylated let-7 miRNA inhibitor to isolate proteins that are involved in let-7 mediated gene regulation that resulted in an affinity purification of Polypyrimidine Tract Binding protein (PTB). Here we show that PTB interacts with miRNAs and human Argonaute 2 (hAgo2) through RNA as well as identified potential mammalian cellular targets that are co-regulated by PTB and hAgo2. In addition, using genetic approach, we have demonstrated that PTB genetically interacts with Caenorhabditis elegans let-7 indicating a conserved role for PTB in miRNA-mediated gene regulation.

Oncogene, 2006

MicroRNAs (miRNAs) are abundant regulatory RNAs involved in the regulation of many key biological... more MicroRNAs (miRNAs) are abundant regulatory RNAs involved in the regulation of many key biological processes. Recent advances in understanding the mechanism of RNA interference and miRNA-mediated mechanisms shed light on major principals of the formation of the regulatory complex and provide models to explain how these small regulatory RNA species interfere with gene expression and how they influence the translational status of the transcriptome.

European Journal of Neuroscience, 2007

Previously, we have established that a product of the doublecortin-like kinase (DCLK) gene, DCLK-... more Previously, we have established that a product of the doublecortin-like kinase (DCLK) gene, DCLK-short, is cleaved by caspases during serum deprivation. Subsequently, the N-terminal cleavage product of DCLK-short facilitates apoptosis in the neuroblastoma cell line NG108. As this N-terminal cleavage product is highly homologous to calcium ⁄ calmodulin-dependent protein kinase-related peptide (CARP), another DCLK gene splice variant, we aimed to determine the possible apoptotic properties of CARP in vivo and in vitro. We report highly specific CARP expression in apoptotic granule cells in the rat dentate gyrus after adrenalectomy relative to healthy granule cells. CARP is significantly upregulated in the suprapyramidal blade of the dentate gyrus, with varying levels of upregulation, depending on the extent of adrenalectomy-induced apoptosis. Similar to the caspase-cleaved N-terminus of DCLKshort, CARP overexpression itself facilitated apoptosis in serum-deprived NG108 cells. Furthermore, CARP facilitated polymerization of tubulin in vitro and was capable of interacting with growth factor receptor-bound protein 2, an intracellular protein involved in vesicle trafficking. Together, our data demonstrate a facilitating role for CARP in the apoptotic process in granule cell populations sensitive to adrenalectomy, and suggest that this proapoptotic effect is mediated by increasing the stability of the microtubule cytoskeleton.

Journal of Neurobiology, 1999

By means of differential display techniques, we have previously identified an mRNA transcript who... more 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 kainateelicited 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 seizureinduced kinases.

Development Genes and Evolution, 2005

Fragile X syndrome is the most common inherited form of mental retardation. It is caused by the l... more Fragile X syndrome is the most common inherited form of mental retardation. It is caused by the lack of the Fragile X Mental Retardation Protein (FMRP), which is encoded by the FMR1 gene. Although Fmr1 knockout mice display some characteristics also found in fragile X patients, it is a complex animal model to study brain abnormalities, especially during early embryonic development. Interestingly, the ortholog of the FMR1 gene has been identified not only in mouse, but also in zebrafish (Danio rerio). In this study, an amino acid sequence comparison of FMRP orthologs was performed to determine the similar regions of FMRP between several species, including human, mouse, frog, fruitfly and zebrafish. Further characterisation of Fmrp has been performed in both adults and embryos of zebrafish using immunohistochemistry and western blotting with specific antibodies raised against zebrafish Fmrp. We have demonstrated a strong Fmrp expression in neurons of the brain and only a very weak expression in the testis. In brain tissue, a different distribution of the isoforms of Fmrp, compared to human and mouse brain tissue, was shown using western blot analysis. Due to the high similarity between zebrafish Fmrp and human FMRP and their similar expression pattern, the zebrafish has great potential as a complementary animal model to study the pathogenesis of the fragile X syndrome, especially during embryonic development.

Molecular Brain Research, 2001

We have recently cloned a novel Doublecortin CaMK-like kinase (rDCAMKL) cDNA, and a related cDNA ... more We have recently cloned a novel Doublecortin CaMK-like kinase (rDCAMKL) cDNA, and a related cDNA called CaMK-related peptide (CARP) from the rat hippocampus. These genes are structurally highly similar to the human DCAMKL-1 gene and doublecortin, a gene associated with X-linked lissencephaly and subcortical band heterotopia. Here we report on the genomic organization of the murine DCAMKL gene and its products. Our results show that DCAMKL and CARP are alternative splice products of the same gene. The DCAMKL gene also generates three alternatively-spliced rDCAMKL transcripts of which we have cloned the corresponding cDNAs and which potentially generate different DCAMKL proteins. In situ hybridization experiments show that the different rDCAMKL transcripts are all expressed in the adult rat hippocampus. We conclude that alternative splicing of the DCAMKL gene may generate different but similar proteins in the adult rat hippocampus thereby regulating different but overlapping aspects of DCAMKL controlled neuronal plasticity.