期刊
JOURNAL OF CELL BIOLOGY
卷 219, 期 6, 页码 -出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201907154
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资金
- European Research Council [ERC StG 281556, CoG 724373]
- Austrian Science Fund (FWF) [P29911, W1250-B20]
- German Research Foundation [DFG SFB1032]
- ISTFELLOW - People Program (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7/2007-2013) under the Research Executive Agency [291734]
- European Molecular Biology Organization [ALTF 1396-2014]
- European Commission (LTFCO-FUND2013) [GA-2013-609409]
- Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) [EXC 2151-390873048]
- American Lebanese Syrian Associated Charities
- Analysis, Imaging and Modelling of Neuronal and Inflammatory Processes graduate school - Ministry of Economics, Science, and Digitisation of the State Saxony-Anhalt
- European Funds for Social and Regional Development
- Austrian Science Fund (FWF) [P29911] Funding Source: Austrian Science Fund (FWF)
Cells navigating through complex tissues face a fundamental challenge: while multiple protrusions explore different paths, the cell needs to avoid entanglement. How a cell surveys and then corrects its own shape is poorly understood. Here, we demonstrate that spatially distinct microtubule dynamics regulate amoeboid cell migration by locally promoting the retraction of protrusions. In migrating dendritic cells, local microtubule depolymerization within protrusions remote from the microtubule organizing center triggers actomyosin contractility controlled by RhoA and its exchange factor Lfc. Depletion of Lfc leads to aberrant myosin localization, thereby causing two effects that rate-limit locomotion: (1) impaired cell edge coordination during path finding and (2) defective adhesion resolution. Compromised shape control is particularly hindering in geometrically complex microenvironments, where it leads to entanglement and ultimately fragmentation of the cell body. We thus demonstrate that microtubules can act as a proprioceptive device: they sense cell shape and control actomyosin retraction to sustain cellular coherence.
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