Directional reorientation of migrating neutrophils is limited by suppression of receptor input signaling at the cell rear through myosin II activity

Amalia Hadjitheodorou, George R. R. Bell, Felix Ellett, Shashank Shastry, Daniel Irimia, Sean R. Collins () and Julie A. Theriot ()
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Amalia Hadjitheodorou: Stanford University
George R. R. Bell: University of California, Davis
Felix Ellett: BioMEMS Resource Center, Massachusetts General Hospital, Harvard Medical School
Shashank Shastry: University of California, Davis
Daniel Irimia: BioMEMS Resource Center, Massachusetts General Hospital, Harvard Medical School
Sean R. Collins: University of California, Davis
Julie A. Theriot: University of Washington

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: 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.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26622-z

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DOI: 10.1038/s41467-021-26622-z

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