Lamins, the nuclear intermediate filaments, are important regulators of nuclear structural integrity as well as nuclear functional processes such as DNA transcription, replication and repair, and epigenetic regulations. A portion of phosphorylated lamin A/C localizes to the nuclear interior in interphase, forming a lamin A/C pool with specific properties and distinct functions. Nucleoplasmic lamin A/C molecular functions are mainly dependent on its binding partners; therefore, revealing new interactions could give us new clues on the lamin A/C mechanism of action. In the present study, we show that lamin A/C interacts with nuclear phosphoinositides (PIPs), and with nuclear myosin I (NM1). Both NM1 and nuclear PIPs have been previously reported as important regulators of gene expression and DNA damage/repair. Furthermore, phosphorylated lamin A/C forms a complex with NM1 in a phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2)-dependent manner in the nuclear interior. Taken together, our study reveals a previously unidentified interaction between phosphorylated lamin A/C, NM1, and PI(4,5)P2 and suggests new possible ways of nucleoplasmic lamin A/C regulation, function, and importance for the formation of functional nuclear microdomains.

• Klíčová slova
• NM1, PI(4,5)P2, cell nucleus, lamin A/C, nuclear lamina, nuclear myosin 1, nucleoplasm, phosphoinositides, phosphorylation,
• MeSH
• buněčné jádro * metabolismus   MeSH
• interfáze MeSH
• intermediární filamenta metabolismus   MeSH
• lamin typ A * metabolismus   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• lamin typ A * MeSH

Nuclear myosin 1 (NM1) has been implicated in key nuclear functions. Together with actin, it has been shown to initiate and regulate transcription, it is part of the chromatin remodeling complex B-WICH, and is responsible for rearrangements of chromosomal territories in response to external stimuli. Here we show that deletion of NM1 in mouse embryonic fibroblasts leads to chromatin and transcription dysregulation affecting the expression of DNA damage and cell cycle genes. NM1 KO cells exhibit increased DNA damage and changes in cell cycle progression, proliferation, and apoptosis, compatible with a phenotype resulting from impaired p53 signaling. We show that upon DNA damage, NM1 forms a complex with p53 and activates the expression of checkpoint regulator p21 (Cdkn1A) by PCAF and Set1 recruitment to its promoter for histone H3 acetylation and methylation. We propose a role for NM1 in the transcriptional response to DNA damage response and maintenance of genome stability.

• MeSH
• apoptóza MeSH
• buněčné jádro účinky léků   genetika   metabolismus   patologie   MeSH
• buněčné linie MeSH
• buněčný cyklus MeSH
• epigeneze genetická MeSH
• etoposid toxicita   MeSH
• genetická transkripce * MeSH
• histonlysin-N-methyltransferasa genetika   metabolismus   MeSH
• inhibitor p21 cyklin-dependentní kinasy genetika   metabolismus   MeSH
• myosin typu I genetika   metabolismus   MeSH
• myši MeSH
• nádorový supresorový protein p53 genetika   metabolismus   MeSH
• poškození DNA * MeSH
• proliferace buněk MeSH
• restrukturace chromatinu * MeSH
• transkripční faktory p300-CBP genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• Cdkn1a protein, mouse MeSH Prohlížeč
• etoposid MeSH
• histonlysin-N-methyltransferasa MeSH
• inhibitor p21 cyklin-dependentní kinasy MeSH
• Myo1c protein, mouse MeSH Prohlížeč
• myosin typu I MeSH
• nádorový supresorový protein p53 MeSH
• Nsccn1 protein, mouse MeSH Prohlížeč
• p300-CBP-associated factor MeSH Prohlížeč
• transkripční faktory p300-CBP MeSH
• Trp53 protein, mouse MeSH Prohlížeč

Plasma membrane tension is an important feature that determines the cell shape and influences processes such as cell motility, spreading, endocytosis and exocytosis. Unconventional class 1 myosins are potent regulators of plasma membrane tension because they physically link the plasma membrane with adjacent cytoskeleton. We identified nuclear myosin 1 (NM1) - a putative nuclear isoform of myosin 1c (Myo1c) - as a new player in the field. Although having specific nuclear functions, NM1 localizes predominantly to the plasma membrane. Deletion of NM1 causes more than a 50% increase in the elasticity of the plasma membrane around the actin cytoskeleton as measured by atomic force microscopy. This higher elasticity of NM1 knock-out cells leads to 25% higher resistance to short-term hypotonic environment and rapid cell swelling. In contrast, overexpression of NM1 in wild type cells leads to an additional 30% reduction of their survival. We have shown that NM1 has a direct functional role in the cytoplasm as a dynamic linker between the cell membrane and the underlying cytoskeleton, regulating the degree of effective plasma membrane tension.

• MeSH
• buněčná membrána metabolismus   MeSH
• buněčné jádro metabolismus   MeSH
• exocytóza fyziologie   MeSH
• fibroblasty cytologie   metabolismus   MeSH
• HeLa buňky MeSH
• kultivované buňky MeSH
• kůže cytologie   metabolismus   MeSH
• lidé MeSH
• mikrofilamenta metabolismus   MeSH
• myosin typu I metabolismus   MeSH
• myši knockoutované MeSH
• myši MeSH
• pohyb buněk MeSH
• tvar buňky MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• myosin typu I MeSH