WASP integrates substrate topology and cell polarity to guide neutrophil migration
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To control their movement, cells need to coordinate actin assembly with the geometric features of their substrate. Here, we uncover a role for the actin regulator WASP in the 3D migration of neutrophils. We show that WASP responds to substrate topology by enriching to sites of inward, substrate-induced membrane deformation. Superresolution imaging reveals that WASP preferentially enriches to the necks of these substrate-induced invaginations, a distribution that could support substrate pinching. WASP facilitates recruitment of the Arp2/3 complex to these sites, stimulating local actin assembly that couples substrate features with the cytoskeleton. Surprisingly, WASP only enriches to membrane deformations in the front half of the cell, within a permissive zone set by WASP’s front-biased regulator Cdc42. While WASP KO cells exhibit relatively normal migration on flat substrates, they are defective at topology-directed migration. Our data suggest that WASP integrates substrate topology with cell polarity by selectively polymerizing actin around substrate-induced membrane deformations in the front half of the cell.
Originalsprog | Engelsk |
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Artikelnummer | e202104046 |
Tidsskrift | Journal of Cell Biology |
Vol/bind | 221 |
Udgave nummer | 2 |
Antal sider | 30 |
ISSN | 0021-9525 |
DOI | |
Status | Udgivet - 7 feb. 2022 |
Bibliografisk note
Publisher Copyright:
© 2021 Brunetti et al.
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