TY - JOUR
T1 - The actin-binding protein PPP1r18 regulates maturation, actin organization, and bone resorption activity of osteoclasts
AU - Matsubara, Takuma
AU - Kokabu, Shoichiro
AU - Nakatomi, Chihiro
AU - Kinbara, Masayuki
AU - Maeda, Toshihiro
AU - Yoshizawa, Mitsuhiro
AU - Yasuda, Hisataka
AU - Takano-Yamamoto, Teruko
AU - Baron, Roland
AU - Jimi, Eijiro
N1 - Funding Information:
This work was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan (KAKENHI 25670870 and 16K20423 to T.M., KAKENHI 23249085 to T.T-Y., and KAKENHI 26293396 to E.J.), the Fukuoka Foundation for Sound
Funding Information:
Health Cancer Research Fund (to T.M.), and the National Institutes of Health (NIAMS R01 AR062054 to R.B.).
Publisher Copyright:
© 2018 American Society for Microbiology.
PY - 2018/2/1
Y1 - 2018/2/1
N2 - 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.
AB - 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.
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U2 - 10.1128/MCB.00425-17
DO - 10.1128/MCB.00425-17
M3 - Article
C2 - 29158294
AN - SCOPUS:85041098719
VL - 38
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
SN - 0270-7306
IS - 4
M1 - e00425-17
ER -