Hepatocellular differentiation status is characterized by distinct subnuclear localization and form of the chanzyme TRPM7
| Autor: | D. Hung Lam, Adenike Ogunrinde, Natalie Beaton, Robyn D. Pereira, Ceredwyn E. Hill, Christiane Whetstone |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Cancer Research Cell type Nucleolus Nuclear Envelope Pyridones Active Transport Cell Nucleus TRPM Cation Channels Rats Sprague-Dawley 03 medical and health sciences Mice Animals Humans Molecular Biology Protein Kinase Inhibitors biology Kinase HEK 293 cells Oncostatin M Cell Differentiation Cell Biology Molecular biology Rats 030104 developmental biology HEK293 Cells Cytoplasm biology.protein Hepatic stellate cell Hepatocytes Benzimidazoles Antibody Cell Nucleolus Developmental Biology |
| Zdroj: | Differentiation; research in biological diversity. 96 |
| ISSN: | 1432-0436 |
| Popis: | The channel-kinase TRPM7 is important for the survival, proliferation, and differentiation, of many cell types. Both plasma membrane channel activity and kinase function are implicated in these roles. Channel activity is greater in less differentiated hepatoma cells compared with non-dividing, terminally differentiated adult hepatocytes, suggesting differences in protein expression and/or localization. We used electrophysiological and immunofluorescence approaches to establish whether hepatocellular differentiation is associated with altered TRPM7 expression. Mean outward current decreased by 44% in WIF-B hepatoma cells incubated with the established hepatic differentiating factors oncostatin M/dexamethasone for 1-8 days. Pre-incubation with pyridone 6, a pan-JAK inhibitor, blocked the current reduction. An antibody targeted to the C-terminus of TRPM7 labelled the cytoplasm in WIF-B cells and intact rat liver. Significant label also localized to the nuclear envelope (NE), with relatively more detected in adult hepatocytes compared with WIF-B cells. Hepatoma cells also exhibited nucleoplasmic labelling with intense signal in the nucleolus. The endogenous labelling pattern closely resembles that of HEK293T cells heterologously expressing a TRPM7 kinase construct containing a putative nucleolar localization sequence. These results suggest that TRPM7 form and distribution between the plasma membrane and nucleus, rather than expression, is altered in parallel with differentiation status in rat hepatic cells. |
| Databáze: | OpenAIRE |
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