Possible role of IRTKS in Tks5-driven osteoclast fusion

Podosomes and invadopodia seen in osteoclasts and cancer cells, respectively, are actin-rich membrane protrusions. We recently demonstrated that an adaptor protein, Tks5, which is an established regulator of invadopodia in cancer cells, drives osteoclast-osteoclast fusion as well as osteoclast-cancer cell fusion by generating circumferential podosomes/invadopodia. This finding revealed an unexpected potential of podosomes/invadopodia to act as fusion-competent protrusions. Fusion of biological membranes involves the intricate orchestration of various proteins and lipids. Recent literature suggests the importance of membrane curvature formation in lipid bilayer fusion. In this study, we investigated the expression of Bin-Amphiphysin-Rvs161/167 (BAR) domain superfamily proteins, which have membrane deforming activity, during osteoclastogenesis. We found that IRTKS was specifically induced during osteoclast fusion and interacted with Tks5, suggesting the role of IRTKS in the formation of fusion-competent protrusions via its BAR domain.