Other Publications (1)
Articles by Jeannine V. Kern in JoVE
Alt hücresel Çözünürlük bozulmamış Drosophila Larva in vivo Görüntüleme Yao Zhang*1,2, Petra Füger*1, Shabab B. Hannan1,2, Jeannine V. Kern1, Bronwen Lasky1, Tobias M. Rasse1 1Junior Research Group Synaptic Plasticity, Hertie Institute for Clinical Brain Research, University of Tübingen, 2Graduate School of Cellular and Molecular Neuroscience, University of Tübingen Bu protokol, bozulmamış anesthetization ve görüntüleme için güvenilir bir yöntem açıklanır
Other articles by Jeannine V. Kern on PubMed
Knockdown of Transactive Response DNA-binding Protein (TDP-43) Downregulates Histone Deacetylase 6 The EMBO Journal. Jan, 2010 | Pubmed ID: 19910924 TDP-43 is an RNA/DNA-binding protein implicated in transcriptional repression and mRNA processing. Inclusions of TDP-43 are hallmarks of frontotemporal dementia and amyotrophic lateral sclerosis. Besides aggregation of TDP-43, loss of nuclear localization is observed in disease. To identify relevant targets of TDP-43, we performed expression profiling. Thereby, histone deacetylase 6 (HDAC6) downregulation was discovered on TDP-43 silencing and confirmed at the mRNA and protein level in human embryonic kidney HEK293E and neuronal SH-SY5Y cells. This was accompanied by accumulation of the major HDAC6 substrate, acetyl-tubulin. HDAC6 levels were restored by re-expression of TDP-43, dependent on RNA binding and the C-terminal protein interaction domains. Moreover, TDP-43 bound specifically to HDAC6 mRNA arguing for a direct functional interaction. Importantly, in vivo validation in TDP-43 knockout Drosophila melanogaster confirmed the specific downregulation of HDAC6. HDAC6 is necessary for protein aggregate formation and degradation. Indeed, HDAC6-dependent reduction of cellular aggregate formation and increased cytotoxicity of polyQ-expanded ataxin-3 were found in TDP-43 silenced cells. In conclusion, loss of functional TDP-43 causes HDAC6 downregulation and might thereby contribute to pathogenesis.