Cited by 29Bone Metabolism and DiseasesBone and Dental Protein StudiesOsteomyelitis and Bone Disorders Research

The Actin-Binding Protein PPP1r18 Regulates Maturation, Actin Organization, and Bone Resorption Activity of Osteoclasts

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Matsubara, Takuma, Kokabu, Shoichiro, Nakatomi, Chihiro, Kinbara, Masayuki, Maeda, Toshihiro, Yoshizawa, Mitsuhiro, Yasuda, Hisataka, Takano-Yamamoto, Teruko +2 more·2018·Molecular and Cellular Biology

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.

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Crossref · 10.1128/mcb.00425-17

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Authors
Matsubara, T., Kokabu, S., Nakatomi, C., Kinbara, M., Maeda, T., Yoshizawa, M., Yasuda, H., Takano-Yamamoto, T., Baron, R., & Jimi, E.
Affiliations
  • Kyushu Dental University (JP)
  • Tohoku University (JP)
  • Oriental Yeast Co., Ltd. (Japan) (JP)
  • Department of Orthodontics and Dentofacial Orthopedics, Graduate School of Dentistry, Tohoku University
  • Harvard University (US)
  • Kyushu University (JP)
Corresponding author
Matsubara, Takuma
Venue
Molecular and Cellular Biology
Published
2018-02-01
Volume
38
Issue
4
ISSN
  • 0270-7306 (ISSN-L)
  • 1098-5549
OpenAlex
W2768779521
Cited by
28
References
50
Citations by year
2026: 3 · 2025: 2 · 2024: 5 · 2023: 3 · 2022: 6 · 2021: 3 · 2019: 6
FWCI
0.67
Type
journal article
Language
en
Open access
Locations
  • Molecular and Cellular Biology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • HHS | National Institutes of Health (R01 AR062054)
  • Ministry of Education, Culture, Sports, Science and Technology (25670870, 16K20423, 23249085, 26293396)
  • Fukuoka Foundation for Sound Health
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
  • Health Sciences › Medicine › Rheumatology › Bone and Dental Protein Studies
  • Health Sciences › Medicine › Rheumatology › Osteomyelitis and Bone Disorders Research
Keywords
osteoclasts, bone resorption, actin rings, actin organization, podosomes, Src family kinases, osteoclastogenesis, sealing zone
MeSH terms
Actins, Animals, Bone Resorption, Cell Adhesion, Cell Differentiation, Cell Line, Humans, Male, Mice, Transgenic, Osteoclasts, Protein Binding, Protein-Tyrosine Kinases, Receptors, Neuropeptide Y, src-Family Kinases, Mice, Dopamine and cAMP-Regulated Phosphoprotein 32, Protein Phosphatase 1

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