Modulation of Tau Subcellular Localization as a Tool to Investigate the Expression of Disease-related Genes
| Autor: | Maria Claudia Caiazza, Valentina Quercioli, Cristina Di Primio, Giacomo Siano, Antonino Cattaneo, Mariantonietta Calvello, Martina Varisco |
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| Přispěvatelé: | Siano, G., Caiazza, M. C., Varisco, M., Calvello, M., Quercioli, V., Cattaneo, A., Di Primio, C. |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Nucleolus
General Chemical Engineering Cellular differentiation Tau protein tau Proteins Biology General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine Alzheimer Disease Cell Line Tumor Humans Gene 030304 developmental biology Cell Nucleus Neurons Regulation of gene expression 0303 health sciences General Immunology and Microbiology General Neuroscience Binding protein Cell Differentiation Subcellular localization RRNA transcription Cell biology Gene Expression Regulation Vesicular Glutamate Transport Protein 1 biology.protein 030217 neurology & neurosurgery Subcellular Fractions |
| Popis: | Tau is a microtubule binding protein expressed in neurons and its main known function is related to the maintenance of cytoskeletal stability. However, recent evidence indicated that Tau is present also in other subcellular compartments including the nucleus where it is implicated in DNA protection, in rRNA transcription, in the mobility of retrotransposons and in the structural organization of the nucleolus. We have recently demonstrated that nuclear Tau is involved in the expression of the VGluT1 gene, suggesting a molecular mechanism that could explain the pathological increase of glutamate release in the early stages of Alzheimer's disease. Until recently, the involvement of nuclear Tau in modulating the expression of target genes has been relatively uncertain and ambiguous due to technical limitations that prevented the exclusion of the contribution of cytoplasmic Tau or the effect of other downstream factors not related to nuclear Tau. To overcome this uncertainty, we developed a method to study the expression of target genes specifically modulated by the nuclear Tau protein. We employed a protocol that couples the use of localization signals and the subcellular fractionation, allowing the exclusion of the interference from the cytoplasmic Tau molecules. Most notably, the protocol is easy and is composed of classic and reliable methods that are broadly applicable to study the nuclear function of Tau in other cell types and cellular conditions. |
| Databáze: | OpenAIRE |
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