RRC ID 65703
著者 Matsubara T, Kokabu S, Nakatomi C, Kinbara M, Maeda T, Yoshizawa M, Yasuda H, Takano-Yamamoto T, Baron R, Jimi E.
タイトル The Actin-Binding Protein PPP1r18 Regulates Maturation, Actin Organization, and Bone Resorption Activity of Osteoclasts.
ジャーナル Mol Cell Biol
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.
巻・号 38(4)
公開日 2018-2-15
DOI 10.1128/MCB.00425-17
PII MCB.00425-17
PMID 29158294
PMC PMC5789032
MeSH Actins / metabolism* Animals Bone Resorption / metabolism* Cell Adhesion / physiology Cell Differentiation / physiology Cell Line Dopamine and cAMP-Regulated Phosphoprotein 32 / metabolism* Humans Male Mice Mice, Transgenic Osteoclasts / cytology* Osteoclasts / metabolism* Protein Binding Protein Phosphatase 1 / metabolism Protein-Tyrosine Kinases / metabolism Receptors, Neuropeptide Y / metabolism src-Family Kinases / metabolism
IF 3.611
リソース情報
ヒト・動物細胞 293(RCB1637)