Phagocytic 'teeth' and myosin-II 'jaw' power target constriction during phagocytosis.


Journal

eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614

Informations de publication

Date de publication:
28 10 2021
Historique:
received: 21 03 2021
accepted: 27 10 2021
pubmed: 29 10 2021
medline: 15 12 2021
entrez: 28 10 2021
Statut: epublish

Résumé

Phagocytosis requires rapid actin reorganization and spatially controlled force generation to ingest targets ranging from pathogens to apoptotic cells. How actomyosin activity directs membrane extensions to engulf such diverse targets remains unclear. Here, we combine lattice light-sheet microscopy (LLSM) with microparticle traction force microscopy (MP-TFM) to quantify actin dynamics and subcellular forces during macrophage phagocytosis. We show that spatially localized forces leading to target constriction are prominent during phagocytosis of antibody-opsonized targets. This constriction is largely driven by Arp2/3-mediated assembly of discrete actin protrusions containing myosin 1e and 1f ('teeth') that appear to be interconnected in a ring-like organization. Contractile myosin-II activity contributes to late-stage phagocytic force generation and progression, supporting a specific role in phagocytic cup closure. Observations of partial target eating attempts and sudden target release via a popping mechanism suggest that constriction may be critical for resolving complex in vivo target encounters. Overall, our findings present a phagocytic cup shaping mechanism that is distinct from cytoskeletal remodeling in 2D cell motility and may contribute to mechanosensing and phagocytic plasticity.

Identifiants

pubmed: 34708690
doi: 10.7554/eLife.68627
pii: 68627
pmc: PMC8585483
doi:
pii:

Substances chimiques

Actins 0
Myosin Type II EC 3.6.1.-

Banques de données

figshare
['10.6084/m9.figshare.16666864', '10.6084/m9.figshare.16677373']

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : NIDDK NIH HHS
ID : R01 DK083345
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM138652
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States

Informations de copyright

© 2021, Vorselen et al.

Déclaration de conflit d'intérêts

DV, SB, YW, WC, JT, NG, MK No competing interests declared

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Auteurs

Daan Vorselen (D)

Department of Biology and Howard Hughes Medical Institute, University of Washington, Seattle, United States.

Sarah R Barger (SR)

Department of Cell and Developmental Biology, State University of New York Upstate Medical University, Syracuse, United States.

Yifan Wang (Y)

Department of Mechanical Engineering, Stanford University, Stanford, United States.

Wei Cai (W)

Department of Mechanical Engineering, Stanford University, Stanford, United States.

Julie A Theriot (JA)

Department of Biology and Howard Hughes Medical Institute, University of Washington, Seattle, United States.

Nils C Gauthier (NC)

IFOM, FIRC Institute of Molecular Oncology, Milan, Italy.

Mira Krendel (M)

Department of Cell and Developmental Biology, State University of New York Upstate Medical University, Syracuse, United States.

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Classifications MeSH