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Journal article
Pannexin 3 ER Ca2+ channel gating is regulated by phosphorylation at the Serine 68 residue in osteoblast differentiation
Scientific reports, v 9(1)
10 Dec 2019
PMID: 31822768
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Pannexin 3 (Panx3) is a regulator of bone formation. Panx3 forms three distinct functional channels: hemichannels, gap junctions, and endoplasmic reticulum (ER) Ca2+ channels. However, the gating mechanisms of the Panx3 channels remain unclear. Here, we show that the Panx3 ER Ca2+ channel is modulated by phosphorylation of the serine 68 residue (Ser68) to promote osteoblast differentiation. Among the 17 candidate phosphorylation sites identified, the mutation of Ser68 to Ala (Ser68Ala) was sufficient to inhibit Panx3-mediated osteoblast differentiation via reduction of Osterix and ALP expression. Using a Ser68 phospho-specific antibody (P-Panx3) revealed Panx3 was phosphorylated in prehypertrophic, hypertrophic chondrocytes, and bone areas of the newborn growth plate. In osteogenic C2C12 cells, P-Panx3 was located on the ER membranes. Importantly, the Ser68Ala mutation only affected Panx3 ER Ca2+ channel function. Ser68 on Panx3 was phosphorylated by ATP stimulation and PI3K/Akt signaling. Finally, real-time FRET imaging and ratio analysis revealed that the Panx3 channel conformation was sensitive to ATP. Together, the phosphorylation of Panx3 at Ser68 is an essential step controlling the gating of the Panx3 ER Ca2+ channel to promote osteogenesis.
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Details
- Title
- Pannexin 3 ER Ca2+ channel gating is regulated by phosphorylation at the Serine 68 residue in osteoblast differentiation
- Creators
- Masaki Ishikawa - Tohoku UniversityGeneva Williams - National Institute of Dental and Craniofacial ResearchPatricia Forcinito - National Institute of Dental and Craniofacial ResearchMomoko Ishikawa - Tohoku UniversityRyan J. Petrie - Drexel UniversityKan Saito - Tohoku UniversitySatoshi Fukumoto - Tohoku UniversityYoshihiko Yamada - National Institute of Dental and Craniofacial Research
- Publication Details
- Scientific reports, v 9(1)
- Publisher
- Springer Nature
- Number of pages
- 14
- Grant note
- LS010 / NEXT program; Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT); Japan Society for the Promotion of Science DE000483-24; DE000483-25; DE000483-26 / Intramural Research Program of the National Institute of Dental and Craniofacial Research, USA 16H05514; 26670880 / Ministry of Education, Science, and Culture of Japan; Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT) Japan Society for the Promotion of Science for Young Scientists; Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT); Japan Society for the Promotion of Science
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biology
- Web of Science ID
- WOS:000502008100001
- Scopus ID
- 2-s2.0-85076441507
- Other Identifier
- 991019167876704721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology