Lamin A/C deficiency enables increased myosin-II bipolar filament ensembles that promote divergent actomyosin network anomalies through self-organization
| Autor: | James R. Bamburg, O'Neil Wiggan, Timothy J. Stasevich, Jennifer G. DeLuca |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Nuclear Envelope
macromolecular substances Biology Cell Line Stress fiber assembly LMNA 03 medical and health sciences 0302 clinical medicine Live cell imaging Cell Line Tumor Myosin Humans Cytoskeleton Molecular Biology Actin 030304 developmental biology Myosin Type II 0303 health sciences Articles Cell Biology Lamin Type A Cell biology Actin Cytoskeleton Gene Expression Regulation Cytoplasm 030217 neurology & neurosurgery Lamin HeLa Cells |
| Zdroj: | Molecular Biology of the Cell |
| ISSN: | 1939-4586 1059-1524 |
| Popis: | Nuclear envelope proteins influence cell cytoarchitecure by poorly understood mechanisms. Here we show that small interfering RNA-mediated silencing of lamin A/C (LMNA) promotes contrasting stress fiber assembly and disassembly in individual cells and within cell populations. We show that LMNA-deficient cells have elevated myosin-II bipolar filament accumulations, irregular formation of actin comet tails and podosome-like adhesions, increased steady state nuclear localization of the mechanosensitive transcription factors MKL1 and YAP, and induced expression of some MKL1/serum response factor-regulated genes such as that encoding myosin-IIA (MYH9). Our studies utilizing live cell imaging and pharmacological inhibition of myosin-II support a mechanism of deregulated myosin-II self-organizing activity at the nexus of divergent actin cytoskeletal aberrations resulting from LMNA loss. In light of our results, we propose a model of how the nucleus, via linkage to the cytoplasmic actomyosin network, may act to control myosin-II contractile behavior through both mechanical and transcriptional feedback mechanisms. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|