Casein kinase-1 isoforms differentially associate with neurofibrillary and granulovacuolar degeneration lesions
| Autor: | Theresa J. Kannanayakal, Jeff Kuret, Haiyang Tao, Dale D. Vandre |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Male
Gene isoform Tau protein Biology Hippocampus Gene Expression Regulation Enzymologic Pathology and Forensic Medicine Cellular and Molecular Neuroscience Alzheimer Disease Antibody Specificity Casein Kinase I Humans Aged 80 and over Peptidylprolyl isomerase Kinase Colocalization Neurofibrillary Tangles Peptidylprolyl Isomerase Immunohistochemistry Molecular biology Isoenzymes NIMA-Interacting Peptidylprolyl Isomerase Biochemistry Nerve Degeneration Vacuoles biology.protein Phosphorylation Female Neurology (clinical) Casein kinase 1 |
| Zdroj: | Acta Neuropathologica. 111:413-421 |
| ISSN: | 1432-0533 0001-6322 |
| DOI: | 10.1007/s00401-006-0049-9 |
| Popis: | Alzheimer's Disease (AD) is characterized by the appearance of neurofibrillary and granulovacuolar lesions in the brains of affected individuals. The former is composed of hyperphosphorylated aggregates of the microtubule-associated protein tau. The latter is poorly characterized but reacts strongly with anti-phosphoepitope antibodies indicating that it too accumulates phosphoproteins. Both lesions react strongly with antibodies directed against members of the casein kinase-1 family of phosphotransferases, a group of closely related protein kinases that frequently function in tandem with the ubiquitin modification system. To determine whether individual members of the casein kinase-1 family differentially associate with AD lesions, hippocampal sections isolated from late stage cases of AD were subjected to double-label fluorescence immunohistochemistry using a panel of selective anti-casein kinase 1 antibodies and small-molecule fluorochromes thioflavin S and thiazin red. The resultant colocalization patterns revealed that the alpha CK1 isoform strongly correlated with thioflavin S and thiazin red fluorescence, indicating that it preferentially associated with neurofibrillary lesions. In contrast, the delta isoform staining pattern was dominated by colocalization with granulovacuolar degeneration bodies. These findings suggest that granulovacuolar and neurofibrillary lesions occupy separate populations of neurons, and implicate CK1 isoforms in the generation of lesion-associated phosphoepitopes. They also suggest a nexus between the phosphorylation and ubiquitination modifications found in both lesions. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink