Mechanotransduction via the LINC complex regulates DNA replication in myonuclei

Wang, Shuoshuo; Stoops, Elizabeth; Cp, Unnikannan; Markus, Barak; Reuveny, Adriana; Ordan, Elly; Volk, Talila

doi:10.1083/jcb.201708137

Cited by 68 publications

(80 citation statements)

References 86 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, reduced BAF levels at the nuclear membrane (induced by D-Titin/sls RNAi) correlated with an increase in DNA content (induced by elevated endoreplication) in these myonuclei. Previously, we reported that reduced BAF levels in muscles led to increased DNA levels in the myonuclei (Wang et al, 2018), whereas here we report that specific reduction of BAF at the nuclear membrane is sufficient for promoting increased DNA replication. Taken together these results demonstrate that BAF localization at the nuclear membrane is mechanosensitive, and might repress DNA endoreplication.…”

Section: Baf Localization At the Nuclear Membrane Depends On Proper Ccontrasting

confidence: 73%

“…Furthermore, this study showed that in the myonuclei of LINC mutant larvae the DNA undergoes additional rounds of DNA replication known as endoreplication, leading to elevated polyploidy (Brayson et al, 2018;Volk, 2012;Wang et al, 2018). These observations implicate the involvement of the LINC complex in the arrest of cell cycle progression in myonuclei of wild-type larvae.…”

Section: Introductionmentioning

confidence: 59%

“…Since we showed previously that BAF transcription is reduced in koi, and klar LINC mutants (Wang et al, 2018), we attempted to rescue BAF localization by its musclespecific overexpression in koi mutant muscles. However, despite an increase in its cytoplasmic levels, BAF overexpression in koi mutants did not rescue its localization at the nuclear membrane (Fig 2 A-B'').…”

Section: Baf Localization At the Nuclear Membrane Depends On Functionmentioning

confidence: 99%

“…In Drosophila muscles, BAF transcription was reported to decrease significantly in mutant larvae lacking Nesprin/Klar or SUN/koi. Furthermore, muscle-specific knock down of BAF phenocopied the increased DNA endoreplication observed in LINC mutant myonuclei (Wang et al, 2018). This led to the hypothesis that BAF acts downstream of the LINC complex-mediated mechanotransduction, to arrest DNA endoreplication in muscles.…”

Section: Introductionmentioning

confidence: 98%

“…In an attempt to reveal components that mediate the LINC-dependent arrest of DNA endoreplication, we performed a screen for genes whose transcription changes in the Nesprin/klar homozygous mutant muscles. One of the identified genes was barrier-to-autointegration factor (baf) (Wang et al, 2018). BAF is a small 89-aa protein, that forms dimmers, which are able to bind dsDNA, and thus capable of bridging between two strands of DNA, and thereby, to potentially affect DNA condensation (Bradley et al, 2005;Zheng et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Mechanosensitive recruitment of BAF to the nuclear membrane inhibits nuclear E2F1 and Yap levels

Unnikannan

Reuveny

Grunberg

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

Mechanotransduction has been implicated as an important factor in regulating cell cycle progression; however, the underlying mechanism has not been fully elucidated.Here, we describe a novel mechano-sensitive component, namely barrier to autointegration factor, (BAF), which regulates DNA endocycling in Drosophila muscle fibers. We show that BAF negatively regulates DNA endoreplication by inhibiting of the nuclear entrance of E2F1 and Yap/Yorkie, two key components in cell cycle control. Furthermore, BAF localization at the nuclear membrane is mechanosensitive, as it was downregulated in LINC mutant larval muscles, or following nuclear deformation caused by disruption of nucleus-sarcomere connections. BAF forms a protein complex with E2F1, which is sensitive to BAF phosphorylation. Knockdown of BAF kinase VRK1/Ball disrupted localization of BAF at the nuclear membrane and resulted in increased E2F1 nuclear levels. Taken together, our results reveal a novel mechanosensitive pathway controlling BAF phosphorylation and localization at the nuclear membrane, which in turn, represses nuclear accumulation of positive cell cycle regulators.

show abstract

Section: Baf Localization At the Nuclear Membrane Depends On Proper Ccontrasting

confidence: 73%

Section: Introductionmentioning

confidence: 59%

Section: Baf Localization At the Nuclear Membrane Depends On Functionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Mechanosensitive recruitment of BAF to the nuclear membrane inhibits nuclear E2F1 and Yap levels

Unnikannan

Reuveny

Grunberg

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

Functions and clinical significance of mechanical tumor microenvironment: cancer cell sensing, mechanobiology and metastasis

Zhou

Wang

Zhang

et al. 2022

Cancer Communications

View full text Add to dashboard Cite

Dynamic and heterogeneous interaction between tumor cells and the surrounding microenvironment fuels the occurrence, progression, invasion, and metastasis of solid tumors. In this process, the tumor microenvironment (TME) fractures cellular and matrix architecture normality through biochemical and mechanical means, abetting tumorigenesis and treatment resistance. Tumor cells sense and respond to the strength, direction, and duration of mechanical cues in the TME by various mechanotransduction pathways. However, far less understood is the comprehensive perspective of the functions and mechanisms of mechanotransduction. Due to the great therapeutic difficulties brought by the mechanical changes in the TME, emerging studies have focused on targeting the adverse mechanical factors in the TME to attenuate disease rather than conventionally targeting tumor cells themselves, which has been proven to be a potential therapeutic approach. In this review, we discussed the origins and roles of mechanical factors in the TME, cell sensing, mechano‐biological coupling and signal transduction, in vitro construction of the tumor mechanical microenvironment, applications and clinical significance in the TME.

show abstract

Physical Stimulation in Tissue-Engineering

Carthew

Shrestha

Donderwinkel

et al. 2019

Tissue Engineering in Oral and Maxillofacial Surgery

View full text Add to dashboard Cite

Mechanotransduction via the LINC complex regulates DNA replication in myonuclei

Abstract: Nuclear mechanotransduction has been implicated in the control of chromatin organization and gene expression. Wang et al. show that, in Drosophila myofibers, the LINC complex is required for the regulation of DNA replication and synchronized cell-cycle progression in myonuclei.

Cited by 68 publications

References 86 publications

Mechanosensitive recruitment of BAF to the nuclear membrane inhibits nuclear E2F1 and Yap levels

Mechanosensitive recruitment of BAF to the nuclear membrane inhibits nuclear E2F1 and Yap levels

Functions and clinical significance of mechanical tumor microenvironment: cancer cell sensing, mechanobiology and metastasis

Physical Stimulation in Tissue-Engineering

Contact Info

Product

Resources

About