Tks5-dependent formation of circumferential podosomes/invadopodia mediates cell-cell fusion.

The Journal of Cell Biology
Tsukasa OikawaKoichi Matsuo

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.

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Citations

Jan 9, 2013·Cellular and Molecular Life Sciences : CMLS·Tsukasa OikawaKoichi Matsuo
Jan 19, 2013·World Journal of Orthopedics·Yukiko Kuroda, Koichi Matsuo
Aug 15, 2014·Cell Death & Disease·K Kolli-BouhafsP Rondé
Oct 8, 2014·The Journal of Cell Biology·Nah-Young ShinRoland Baron
Jul 25, 2014·Journal of Cellular Physiology·Jiro TakitoMasanori Nakamura
Oct 9, 2015·Molecular Biology of the Cell·Serisha MoodleyMingyao Liu
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Apr 10, 2014·Cell Adhesion & Migration·Christine M Gould, Sara A Courtneidge
Jun 7, 2013·Communicative & Integrative Biology·Tsukasa Oikawa, Koichi Matsuo
Sep 27, 2013·JAK-STAT·Takeshi Miyamoto
Dec 21, 2014·Bone·Kent SøeJean-Marie Delaisse
Oct 21, 2016·Journal of Cellular Physiology·Anaïs Marie Julie MøllerKent Søe
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Sep 16, 2020·International Journal of Molecular Sciences·Jiro Takito, Masanori Nakamura
Feb 3, 2021·Experimental Cell Research·Chia-Hsiao KuoYing-Ming Liou

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Methods Mentioned

BETA
immunoprecipitation
PCR
transfection
confocal microscopy
acetylation

Software Mentioned

Mascot
GeneSpring GX
FluoView FV10i
ImageJ
FluoView
LSM
LAS AF

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