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Spatiotemporal control of actomyosin contractility by MRCKβ signaling drives phagocytosis

Zihni, Ceniz; Georgiadis, Anastasios; Ramsden, Conor M; Sanchez-Heras, Elena; Haas, Alexis J; Nommiste, Britta; Semenyuk, Olha; ... Matter, Karl; + view all (2022) Spatiotemporal control of actomyosin contractility by MRCKβ signaling drives phagocytosis. Journal of Cell Biology , 221 (11) , Article e202012042. 10.1083/jcb.202012042. Green open access

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Abstract

Phagocytosis requires actin dynamics, but whether actomyosin contractility plays a role in this morphodynamic process is unclear. Here, we show that in the retinal pigment epithelium (RPE), particle binding to Mer Tyrosine Kinase (MerTK), a widely expressed phagocytic receptor, stimulates phosphorylation of the Cdc42 GEF Dbl3, triggering activation of MRCKβ/myosin-II and its coeffector N-WASP, membrane deformation, and cup formation. Continued MRCKβ/myosin-II activity then drives recruitment of a mechanosensing bridge, enabling cytoskeletal force transmission, cup closure, and particle internalization. In vivo, MRCKβ is essential for RPE phagocytosis and retinal integrity. MerTK-independent activation of MRCKβ signaling by a phosphomimetic Dbl3 mutant rescues phagocytosis in retinitis pigmentosa RPE cells lacking functional MerTK. MRCKβ is also required for efficient particle translocation from the cortex into the cell body in Fc receptor-mediated phagocytosis. Thus, conserved MRCKβ signaling at the cortex controls spatiotemporal regulation of actomyosin contractility to guide distinct phases of phagocytosis in the RPE and represents the principle phagocytic effector pathway downstream of MerTK.

Type: Article
Title: Spatiotemporal control of actomyosin contractility by MRCKβ signaling drives phagocytosis
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1083/jcb.202012042
Publisher version: https://doi.org/10.1083/jcb.202012042
Language: English
Additional information: © 2022 Zihni et al. This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
Keywords: Actins, Actomyosin, Myosin Type II, Myotonin-Protein Kinase, Phagocytosis, Protein-Tyrosine Kinases, Receptors, Fc, c-Mer Tyrosine Kinase
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10156375
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