Elk-1 interacts with neuronal microtubules and relocalizes to the nucleus upon phosphorylation |
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| Authors: | Ozlem Demir Sirin Korulu Aysegul Yildiz Arzu Karabay Isil Aksan Kurnaz |
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| Affiliation: | 1. Yeditepe University, Department of Genetics and Bioengineering, 26 Agustos Yerlesimi, 34755, Kayisdagi, Istanbul, Turkey;2. Istanbul Technical University, Department of Molecular Biology and Genetics, Maslak, Istanbul, Turkey;1. MRC Clinical Sciences Centre, Imperial College London, Du Cane Road, London W12 0NN, UK;1. Department of Neurology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA;2. Department of Neurosciences, University of New Mexico Health Sciences Center, Albuquerque, NM, USA;1. Department of Cancer Medicine, Gustave Roussy Institute, Cancer Campus, Grand Paris, University of Paris-Sud, Villejuif, France;2. Institut Jean Godinot, Reims, France;1. Institute of Physiology, Academy of Sciences of the Czech Republic, v.v.i., Vídeňská 1083, 142 20 Prague 4, Czech Republic;2. Department of Physiology, Faculty of Science, Charles University, Vini?ná 7, 120 00 Prague, Czech Republic;3. Third Surgical Department, First Faculty of Medicine, Charles University, V Úvalu 84, 150 06 Prague, Czech Republic;3. Departments of Pediatrics;4. Departments of Internal Medicine, Children''s Hospital of Pittsburgh of UPMC, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15224;5. Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama 35213 |
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| Abstract: | ETS domain transcription factor Elk-1 has been primarily studied in the regulation of genes in response to mitogenic stimuli, however the presence of Elk-1 in axonal projections of largely post-mitotic adult hippocampal sections has been reported. This finding has initially led us to a basic question: how is Elk-1 anchored to neuronal projections? To that end, we have investigated the intracellular localization of Elk-1 and its biochemical interactions with neuronal microtubules in model systems. Our results showed co-localization of Elk-1 with microtubules in hippocampal cultures and SH-SY5Y neuroblastoma cell lines, and have further demonstrated that Elk-1 protein can biochemically interact with microtubules in vitro. Analysis of the protein sequence has indicated many putative microtubule binding domains, with the strongest binding prediction in amino acids 314–325, and our results show that Elk-1 can bind to microtubules through most of these regions, but no interaction was observed through the DNA binding domain, where no putative binding motifs were predicted. We further show that upon serum induction, most of the phospho-Elk-1 translocates to the nucleus, which is independent of translation. We propose that Elk-1 is anchored to neuronal microtubules in resting or unstimulated cells, and upon stimulation is phosphorylated, which relocalizes phospho-Elk-1 to the nucleus in neurons. |
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