@article {64784,
	title = {An actin-based protrusion originating from a podosome-enriched region initiates macrophage fusion.},
	journal = {Molecular Biology of the Cell},
	volume = {30},
	year = {2019},
	month = {2019 Aug 1},
	pages = {2254-67},
	abstract = {<p>Macrophage fusion resulting in the formation of multinucleated giant cells occurs in a variety of chronic inflammatory diseases, yet the mechanism responsible for initiating macrophage fusion is unknown. Here, we used live cell imaging to show that actin-based protrusions at the leading edge initiate macrophage fusion. Phase contrast video microscopy demonstrated that in the majority of events, short protrusions (3 {\textpm} 1 μm) between two closely apposed cells initiated fusion, but occasionally we observed long protrusions (16 {\textpm} 7 μm). Using macrophages isolated from LifeAct mice and imaging with lattice light sheet microscopy, we further found that fusion-competent actin-based protrusions formed at sites enriched in podosomes. Inducing fusion in mixed populations of GFP- and mRFP-LifeAct macrophages showed rapid spatial overlap between GFP and RFP signal at the site of fusion. Cytochalasin B strongly reduced fusion and when rare fusion events occurred, protrusions were not observed. Fusion of macrophages deficient in Wiskott-Aldrich syndrome protein and Cdc42, key molecules involved in the formation of actin-based protrusions and podosomes, was also impaired both in vitro and in vivo. Finally, inhibiting the activity of the Arp2/3 complex decreased fusion and podosome formation. Together these data indicate that an actin-based protrusion formed at the leading edge macrophage fusion.</p>
},
	doi = {10.1101/538314},
	author = {Faust, James J and Balabiyev, Arnat and Heddleston, John M and Podolnikova, Nataly P and Baluch, Debra Page and Chew, Teng-Leong and Ugarova, Tatiana P}
}
