The actin-binding protein PPP1r18 regulates maturation, actin organization, and bone resorption activity of osteoclasts

Takuma Matsubara, Shoichiro Kokabu, Chihiro Nakatomi, Masayuki Kinbara, Toshihiro Maeda, Mitsuhiro Yoshizawa, Hisataka Yasuda, Teruko Takano-Yamamoto, Roland Baron, Eijiro Jimi

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4 Citations (Scopus)

Abstract

Osteoclasts resorb bone by attaching on the bone matrix and forming a sealing zone. In Src-deficient mice, osteoclasts cannot form the actin ring, a characteristic actin structure that seals the resorbed area, and resorb hardly any bone as a result. However, the molecular mechanism underlying the role of Src in the regulation and organization of the actin ring is still unclear. We identified an actin-regulatory protein, protein phosphatase 1 regulatory subunit 18 (PPP1r18), as an Src-binding protein in an Src-, Yes-, and Fyn-deficient fibroblast (SYF) cell line overexpressing a constitutively active form of Src. PPP1r18 was localized in the nucleus and actin ring. PPP1r18 overexpression in osteoclasts inhibited terminal differentiation, actin ring formation, and bone-resorbing activity. A mutation of the protein phosphatase 1 (PP1)-binding domain of PPP1r18 rescued these phenotypes. In contrast, PPP1r18 knockdown promoted terminal differentiation and actin ring formation. In summary, we showed that PPP1r18 likely plays a role in podosome organization and bone resorption.

Original languageEnglish
Article numbere00425-17
JournalMolecular and cellular biology
Volume38
Issue number4
DOIs
Publication statusPublished - Feb 1 2018

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All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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