Binding of Y-P30 to syndecan 2/3 regulates the nuclear localization of CASK
| Autor: | Landgraf, P., Mikhaylova, Marina, Macharadze, T., Borutzki, C., Zenclussen, A.C., Wahle, P., Kreutz, M.R., Sub Cell Biology, Celbiologie |
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| Přispěvatelé: | Sub Cell Biology, Celbiologie |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Time Factors
viruses Gene Expression lcsh:Medicine Pleiotrophin Biochemistry Syndecan 1 Molecular Cell Biology Neurobiology of Disease and Regeneration Chlorocebus aethiops lcsh:Science Cells Cultured Neurons Gene knockdown Multidisciplinary Neuronal Morphology Reverse Transcriptase Polymerase Chain Reaction Molting Developmental neuroscience Messenger RNA Immunoblotting Gene expression Neurites Axons Neurochemistry Animal Models medicine.anatomical_structure COS Cells RNA Interference Research Article Protein Binding Neurite Blotting Western Green Fluorescent Proteins Nerve Tissue Proteins Biology Signaling Pathways Receptors N-Methyl-D-Aspartate Model Organisms Developmental Neuroscience medicine Animals Humans Rats Long-Evans CASK Transcription factor Cell Nucleus lcsh:R Proteins Molecular biology Rats Cell nucleus HEK293 Cells Microscopy Fluorescence Cellular Neuroscience Rat Syndecan-3 lcsh:Q Molecular Neuroscience Syndecan-2 Peptides T-Box Domain Proteins Guanylate Kinases Nuclear localization sequence Neuroscience |
| Zdroj: | PLoS ONE, Vol 9, Iss 2, p e85924 (2014) PLOS ONE, 9(2): e85924 PLoS One, 9(2). Public Library of Science PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | The survival promoting peptide Y-P30 has documented neuroprotective effects as well as cell survival and neurite outgrowth promoting activity in vitro and in vivo. Previous work has shown that multimerization of the peptide with pleiotrophin (PTN) and subsequent binding to syndecan (SDC) -2 and -3 is involved in its neuritogenic effects. In this study we show that Y-P30 application regulates the nuclear localization of the SDC binding partner Calcium/calmodulin-dependent serine kinase (CASK) in neuronal primary cultures during development. In early development at day in vitro (DIV) 8 when mainly SDC-3 is expressed supplementation of the culture medium with Y-P30 reduces nuclear CASK levels whereas it has the opposite effect at DIV 18 when SDC-2 is the dominant isoform. In the nucleus CASK regulates gene expression via its association with the T-box transcription factor T-brain-1 (Tbr-1) and we indeed found that gene expression of downstream targets of this complex, like the GluN2B NMDA-receptor, exhibits a corresponding down- or up-regulation at the mRNA level. The differential effect of Y-P30 on the nuclear localization of CASK correlates with its ability to induce shedding of the ectodomain of SDC-2 but not -3. shRNA knockdown of SDC-2 at DIV 18 and SDC-3 at DIV 8 completely abolished the effect of Y-P30 supplementation on nuclear CASK levels. During early development a protein knockdown of SDC-3 also attenuated the effect of Y-P30 on axon outgrowth. Taken together these data suggest that Y-P30 can control the nuclear localization of CASK in a SDC-dependent manner. |
| Databáze: | OpenAIRE |
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