Mechanical stimulation induces formin-dependent assembly of a perinuclear actin rim.
Cells constantly sense and respond to mechanical signals by reorganizing their actin cytoskeleton. Although a number of studies have explored the effects of mechanical stimuli on actin dynamics, the immediate response of actin after force application has not been studied. We designed a method to monitor the spatiotemporal reorganization of actin after cell stimulation by local force application. We found that force could induce transient actin accumulation in the perinuclear region within ∼ 2 min. This actin reorganization was triggered by an intracellular Ca(2+) burst induced by force application. Treatment with the calcium ionophore A23187 recapitulated the force-induced perinuclear actin remodeling. Blocking of actin polymerization abolished this process. Overexpression of Klarsicht, ANC-1, Syne Homology (KASH) domain to displace nesprins from the nuclear envelope did not abolish Ca(2+)-dependent perinuclear actin assembly. However, the endoplasmic reticulum- and nuclear membrane-associated inverted formin-2 (INF2), a potent actin polymerization activator (mutations of which are associated with several genetic diseases), was found to be important for perinuclear actin assembly. The perinuclear actin rim structure colocalized with INF2 on stimulation, and INF2 depletion resulted in attenuation of the rim formation. Our study suggests that cells can respond rapidly to external force by remodeling perinuclear actin in a unique Ca(2+)- and INF2-dependent manner.
Mechanobiology Institute, National University of Singapore, 117411 Singapore;
Xiaowei
X
Shao
Mechanobiology Institute, National University of Singapore, 117411 Singapore;
Qingsen
Q
Li
Courant Institute and Department of Biology, New York University, New York, NY 10012;
Alex
A
Mogilner
Mechanobiology Institute, National University of Singapore, 117411 Singapore; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel; alexander.bershadsky@weizmann.ac.il shiva.gvs@gmail.com.
Alexander D
AD
Bershadsky
Mechanobiology Institute, National University of Singapore, 117411 Singapore; Department of Biological Sciences, National University of Singapore, 117543 Singapore; and FIRC Institute of Molecular Oncology, Milan 20139, Italy alexander.bershadsky@weizmann.ac.il shiva.gvs@gmail.com.
G V
GV
Shivashankar
D008841:Actin Cytoskeleton / Q000502:physiology* / Q000648:ultrastructure; D000818:Animals; D001696:Biomechanical Phenomena; D002118:Calcium / Q000378:metabolism; D002467:Cell Nucleus / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D000080865:Formins; D015151:Immunoblotting; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism; D018625:Microscopy, Atomic Force; D041681:NIH 3T3 Cells; D010812:Physical Stimulation
D000080865:Formins; C515509:INF2 protein, mouse; D008840:Microfilament Proteins; D002118:Calcium
calcium; force; formin; mechanotransduction; perinuclear actin rim