2022
DOI: 10.1016/j.devcel.2021.11.024
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WASp triggers mechanosensitive actin patches to facilitate immune cell migration in dense tissues

Abstract: Summary When crawling through the body, leukocytes often traverse tissues that are densely packed with extracellular matrix and other cells, and this raises the question: How do leukocytes overcome compressive mechanical loads? Here, we show that the actin cortex of leukocytes is mechanoresponsive and that this responsiveness requires neither force sensing via the nucleus nor adhesive interactions with a substrate. Upon global compression of the cell body as well as local indentation of the plasma m… Show more

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Cited by 62 publications
(64 citation statements)
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References 92 publications
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“…Actin filament orientation is important for function, as myosin sliding along linear actin bundles for effective contraction requires a ring geometry with mixed actin filament polarities (Blanchoin et al, 2014; Cheffings et al, 2016). Our findings are also consistent with studies demonstrating a role for WASP in forming actin structures orthogonal to the cell’ s plasma membrane (Gaertner et al, 2022), as well as polarity during hemocyte (Stramer et al, 2005) and neutrophil (Brunetti et al, 2022) migration. Loss of branched actin also led to the formation of long linear actin filament bundles in the center of the wound.…”
Section: Discussionsupporting
confidence: 92%
“…Actin filament orientation is important for function, as myosin sliding along linear actin bundles for effective contraction requires a ring geometry with mixed actin filament polarities (Blanchoin et al, 2014; Cheffings et al, 2016). Our findings are also consistent with studies demonstrating a role for WASP in forming actin structures orthogonal to the cell’ s plasma membrane (Gaertner et al, 2022), as well as polarity during hemocyte (Stramer et al, 2005) and neutrophil (Brunetti et al, 2022) migration. Loss of branched actin also led to the formation of long linear actin filament bundles in the center of the wound.…”
Section: Discussionsupporting
confidence: 92%
“…Although the overall speed of both imDCs and mDCs was reduced, which is consistent with previous studies ( Extended data Fig. 10b ) 14,3032 , the FP mode was absent, and the mean speed of both SD and SP modes was decreased significantly for both cases of myosin II and Arp2/3 inhibition ( Fig. 4d ).…”
supporting
confidence: 91%
“…Arp2/3 complex activation in leukocytes is multi-faceted. The WAVE regulatory complex is fundamentally linked to traveling waves that drive lamellipodial protrusion and phagocytosis [ 62 , 63 , 64 ]. WASP, on the other hand, seems to have a more localized effect, exemplified by its role in podosome function [ 29 ] and endocytosis [ 30 , 65 ].…”
Section: Discussionmentioning
confidence: 99%
“…WASP, on the other hand, seems to have a more localized effect, exemplified by its role in podosome function [ 29 ] and endocytosis [ 30 , 65 ]. WASP appears to respond to localized signals, including physical force and surface topography [ 62 , 66 ]. Despite these discrete contributions in some contexts, recent evidence also points to a role for both WAVE and WASP in pseudopod-based motility [ 67 ].…”
Section: Discussionmentioning
confidence: 99%