Role of actin dependent nuclear deformation in regulating early gene expression

• Published in: PloS one 2012-12, Vol.7 (12), p.e53031-e53031
• Main Authors: Gupta, Soumya, Marcel, Nimi, Sarin, Apurva, Shivashankar, G V
• Format: Article
• Language: English
• Subjects: Actin; Actins - metabolism; Actins - physiology; Alterations; Animals; Antigens; Beads; Biology; CD69 antigen; Cell activation; Cell Nucleus - metabolism; Cell Nucleus - physiology; Cell Nucleus Shape - genetics; Cell Nucleus Shape - physiology; Deformation; Depolymerization; Elongation; Experiments; Extracellular signal-regulated kinase; Fibroblasts; Fibronectin; Fibronectins; Flow cytometry; Gene expression; Gene Expression Regulation - physiology; Genes; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; Immobilization; Immunology; Inhibition; Intermediates; Kinases; Lymphocyte Activation - genetics; Lymphocyte Activation - physiology; Lymphocytes; Lymphocytes T; Mice; Mice, Inbred C57BL; Mice, Transgenic; Models, Biological; Muscle proteins; NF-κB protein; NIH 3T3 Cells; Nuclear deformation; Nuclei; Nuclei (cytology); Physiological aspects; Physiology; Polymerization; Rodents; Signaling; Stem cells; Stress, Mechanical; T cells; T-Lymphocytes - metabolism; T-Lymphocytes - physiology; T-Lymphocytes - ultrastructure; Tenascin; Tenascin C; Time Factors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0053031

The nucleus of a living cell is constantly undergoing changes in shape and size as a result of various mechanical forces in physiology. These changes correlate with alterations in gene expression, however it is unclear whether nuclear deformation alone is sufficient to elicit these alterations. We used T-cell activation as a model system to test the coupling between nuclear deformation (elongation) and gene expression. Naïve T-cell activation with surrogate antigens resulted in actin dependent nuclear elongation. This was accompanied with Erk and NF-κB signaling to the nucleus to induce CD69 expression. Importantly, inhibiting actin polymerization abolished both nuclear elongation and CD69 expression, while inhibiting Erk, NF-κB or microtubule depolymerization only abolished expression but not elongation. Immobilization of antigen-coated beads, under conditions where actin polymerization was inhibited, rescued both nuclear elongation and CD69 expression. In addition, fibroblast cells plated on fibronectin micropatterns of different sizes showed correlation between nuclear shape index and tenascin C expression. Upon inhibiting the signaling intermediate Erk, tenascin C expression was down regulated although the nuclear shape index remained unaltered. Our results highlight the importance of specific signaling intermediates accompanied with nuclear deformation in the modulation of cellular genomic programs.