Dynamic force-induced direct dissociation of protein complexes in a nuclear body in living cells.
Despite past progress in understanding mechanisms of cellular mechanotransduction, it is unclear whether a local surface force can directly alter nuclear functions without intermediate biochemical cascades. Here we show that a local dynamic force via integrins results in direct displacements of coilin and SMN proteins in Cajal bodies and direct dissociation of coilin-SMN associated complexes. Spontaneous movements of coilin increase more than those of SMN in the same Cajal body after dynamic force application. Fluorescence resonance energy transfer changes of coilin-SMN depend on force magnitude, an intact F-actin, cytoskeletal tension, Lamin A/C, or substrate rigidity. Other protein pairs in Cajal bodies exhibit different magnitudes of fluorescence resonance energy transfer. Dynamic cyclic force induces tiny phase lags between various protein pairs in Cajal bodies, suggesting viscoelastic interactions between them. These findings demonstrate that dynamic force-induced direct structural changes of protein complexes in Cajal bodies may represent a unique mechanism of mechanotransduction that impacts on nuclear functions involved in gene expression.
Department of Mechanical Science and Engineering, University of Illinois at Urbana-Champaign, IL 61801, USA.
Yeh-Chuin
YC
Poh
Sergey P
SP
Shevtsov
Farhan
F
Chowdhury
Douglas C
DC
Wu
Sungsoo
S
Na
Miroslav
M
Dundr
Ning
N
Wang
D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D020541:Coiled Bodies / Q000378:metabolism*; D031541:Fluorescence Resonance Energy Transfer; D006367:HeLa Cells; D006801:Humans; D034904:Lamin Type A / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D051190:Plectin / Q000235:genetics / Q000378:metabolism
D000199:Actins; C494847:LMNA protein, human; D034904:Lamin Type A; D009687:Nuclear Proteins; D051190:Plectin; C440308:lamin C; C068921:p80-coilin