PMID:22584907

Citation	Oikawa, T, Oyama, M, Kozuka-Hata, H, Uehara, S, Udagawa, N, Saya, H and Matsuo, K (2012) Tks5-dependent formation of circumferential podosomes/invadopodia mediates cell-cell fusion. J. Cell Biol. 197:553-68
Abstract	Osteoclasts fuse to form multinucleated cells during osteoclastogenesis. This process is mediated by dynamic rearrangement of the plasma membrane and cytoskeleton, and it requires numerous factors, many of which have been identified. The underlying mechanism remains obscure, however. In this paper, we show that Tks5, a master regulator of invadopodia in cancer cells, is crucial for osteoclast fusion downstream of phosphoinositide 3-kinase and Src. Expression of Tks5 was induced during osteoclastogenesis, and prevention of this induction impaired both the formation of circumferential podosomes and osteoclast fusion without affecting cell differentiation. Tyrosine phosphorylation of Tks5 was attenuated in Src-/- osteoclasts, likely accounting for defects in podosome organization and multinucleation in these cells. Circumferential invadopodia formation in B16F0 melanoma cells was also accompanied by Tks5 phosphorylation. Co-culture of B16F0 cells with osteoclasts in an inflammatory milieu promoted the formation of melanoma-osteoclast hybrid cells. Our results thus reveal an unexpected link between circumferential podosome/invadopodium formation and cell-cell fusion in and beyond osteoclasts.
Links	PubMed PMC3352951 Online version:10.1083/jcb.201111116
Keywords	Adaptor Proteins, Vesicular Transport/genetics; Adaptor Proteins, Vesicular Transport/metabolism; Animals; Cell Differentiation; Cell Fusion; Cell Line, Tumor; Humans; Mice; Osteoclasts/metabolism; Phosphoproteins/genetics; Phosphoproteins/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:SPD2A		GO:0072675: osteoclast fusion	ECO:0000315:		P		Figure 3, Figure 4 and Figure 5.	complete CACAO 6711
HUMAN:SPD2A	involved_in	GO:0072675: osteoclast fusion	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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