WASP integrates substrate topology and cell polarity to guide neutrophil migration.
J Cell Biol
; 221(2)2022 02 07.
Article
en En
| MEDLINE
| ID: mdl-34964841
ABSTRACT
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Movimiento Celular
/
Polaridad Celular
/
Proteína del Síndrome de Wiskott-Aldrich
/
Neutrófilos
Límite:
Humans
Idioma:
En
Revista:
J Cell Biol
Año:
2022
Tipo del documento:
Article
País de afiliación:
Canadá