An actin-based protrusion originating from a podosome-enriched region initiates macrophage fusion

Podosome Cell fusion Multinucleate Live cell imaging Fusion mechanism Wiskott–Aldrich syndrome protein
DOI: 10.1091/mbc.e19-01-0009 Publication Date: 2019-06-26T17:18:43Z
ABSTRACT
Macrophage fusion resulting in the formation of multinucleated giant cells occurs a variety chronic inflammatory diseases, yet mechanism responsible for initiating this process is unknown. Here, we used live cell imaging to show that actin-based protrusions at leading edge initiate macrophage fusion. Phase-contrast video microscopy demonstrated majority events, short (∼3 µm) between two closely apposed initiated fusion, but occasionally observed long (∼12 µm). Using macrophages isolated from LifeAct mice and with lattice light sheet microscopy, further found fusion-competent formed sites enriched podosomes. Inducing mixed populations GFP- mRFP-LifeAct showed rapid spatial overlap GFP RFP signal site Cytochalasin B strongly reduced when rare events occurred, were not observed. Fusion deficient Wiskott-Aldrich syndrome protein Cdc42, key molecules involved podosomes, was also impaired both vitro vivo. Finally, inhibiting activity Arp2/3 complex decreased podosome formation. Together these data suggest an protrusion initiates
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