肌球蛋白
细胞生物学
光遗传学
受体
罗亚
生物
电池极性
信号转导
细胞
神经科学
生物化学
作者
Amalia Hadjitheodorou,George R. R. Bell,Felix Ellett,S. V. S. Shastry,Daniel Irimia,Sean R. Collins,Julie A. Theriot
标识
DOI:10.1038/s41467-021-26622-z
摘要
Abstract To migrate efficiently to target locations, cells must integrate receptor inputs while maintaining polarity: a distinct front that leads and a rear that follows. Here we investigate what is necessary to overwrite pre-existing front-rear polarity in neutrophil-like HL60 cells migrating inside straight microfluidic channels. Using subcellular optogenetic receptor activation, we show that receptor inputs can reorient weakly polarized cells, but the rear of strongly polarized cells is refractory to new inputs. Transient stimulation reveals a multi-step repolarization process, confirming that cell rear sensitivity to receptor input is the primary determinant of large-scale directional reversal. We demonstrate that the RhoA/ROCK/myosin II pathway limits the ability of receptor inputs to signal to Cdc42 and reorient migrating neutrophils. We discover that by tuning the phosphorylation of myosin regulatory light chain we can modulate the activity and localization of myosin II and thus the amenability of the cell rear to ‘listen’ to receptor inputs and respond to directional reprogramming.
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