A Protein Kinase, PKN, Accumulates in Alzheimer Neurofibrillary Tangles and Associated Endoplasmic Reticulum-Derived Vesicles and Phosphorylates Tau Protein
| Autor: | Taizo Taniguchi, Chikako Tanaka, Kiyoshi Maeda, Hideyuki Mukai, Takeshi Hashimoto, Yoshitaka Ono, Michinori Kitagawa, Toshio Kawamata |
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| Rok vydání: | 1998 |
| Předmět: |
Male
Tau protein tau Proteins Endoplasmic Reticulum Antibodies Article symbols.namesake Alzheimer Disease medicine Animals Humans Senile plaques Phosphorylation Protein Kinase C Protein kinase C Aged Aged 80 and over Brain Chemistry Neurons biology Kinase General Neuroscience Endoplasmic reticulum Neurodegeneration Neurofibrillary Tangles Intracellular Membranes Middle Aged Golgi apparatus medicine.disease Cell Compartmentation Cell biology Microscopy Electron Biochemistry Cytoplasm symbols biology.protein Female Rabbits Subcellular Fractions |
| Zdroj: | ResearcherID |
| ISSN: | 1529-2401 0270-6474 |
| Popis: | A possible role for a protein kinase, PKN, a fatty acid-activated serine/threonine kinase with a catalytic domain homologous to the protein kinase C family and a direct target for Rho, was investigated in the pathology of Alzheimer’s disease (AD) using a sensitive immunocytochemistry on postmortem human brain tissues and a kinase assay for human tau protein. The present study provides evidences by light, electron, and confocal laser microscopy that in control human brains, PKN is enriched in neurons, where the kinase is concentrated in a subset of endoplasmic reticulum (ER) and ER-derived vesicles localized to the apical compartment of juxtanuclear cytoplasm, as well as late endosomes, multivesicular bodies, Golgi bodies, secretary vesicles, and nuclei. In AD-affected neurons, PKN was redistributed to the cortical cytoplasm and neurites and was closely associated with neurofibrillary tangles (NFTs) and their major constituent, abnormally modified tau. PKN was also found in degenerative neurites within senile plaques. In addition, we report that human tau protein is directly phosphorylated by PKN bothin vitroandin vivo. Thus, our results suggest a specific role for PKN in NFT formation and neurodegeneration in AD damaged neurons. |
| Databáze: | OpenAIRE |
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