Cofilin is required for polarization of tension in stress fiber networks during migration.
Stacey LeeSanjay KumarPublished in: Journal of cell science (2020)
Cell migration is associated with the establishment of defined leading and trailing edges, which in turn requires polarization of contractile forces. While the actomyosin stress fiber (SF) network plays a critical role in enforcing this polarity, precisely how this asymmetry is established remains unclear. Here, we provide evidence for a model in which the actin-severing protein cofilin (specifically cofilin-1) participates in symmetry breakage by removing low-tension actomyosin filaments during transverse arc assembly. Cofilin knockdown (KD) produces a non-polarized SF architecture that cannot be rescued with chemokines or asymmetric matrix patterns. Whereas cofilin KD increases whole-cell prestress, it decreases prestress within single SFs, implying an accumulation of low-tension SFs. This notion is supported by time-lapse imaging, which reveals weakly contractile and incompletely fused transverse arcs. Confocal and super-resolution imaging further associate this failed fusion with the presence of crosslinker-rich, tropomyosin-devoid nodes at the junctions of multiple transverse arc fragments and dorsal SFs. These results support a model in which cofilin facilitates the formation of high-tension transverse arcs, thereby promoting mechanical asymmetry.
Keyphrases
- cell migration
- high resolution
- skeletal muscle
- spinal cord
- smooth muscle
- squamous cell carcinoma
- single cell
- cell therapy
- spinal cord injury
- radiation therapy
- stem cells
- stress induced
- mass spectrometry
- small molecule
- fluorescent probe
- rectal cancer
- photodynamic therapy
- amino acid
- single molecule
- quantum dots
- mesenchymal stem cells
- heat stress
- sentinel lymph node