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bioRxiv · 10.1101/2020.07.10.197731

Lamin A/C Deficiency Enables Increased Myosin2 Bipolar Filament Ensembles Which Promote Divergent Actomyosin Network Anomalies Through Self Organization

O'Neil Wiggan·Jennifer G DeLuca·Timothy J Stasevich·James R Bamburg
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Abstract

Nuclear envelope proteins influence cell cytoarchitecure by poorly understood mechanisms. Here we show that siRNA-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 (SRF) 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 resultant 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.

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O'Neil Wiggan, Jennifer G DeLuca, Timothy J Stasevich, James R Bamburg. 2020-07-10. Lamin A/C Deficiency Enables Increased Myosin2 Bipolar Filament Ensembles Which Promote Divergent Actomyosin Network Anomalies Through Self Organization. https://doi.org/10.1101/2020.07.10.197731

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