ArticleBMC cell biology2004
Polyphosphoinositides-dependent regulation of the osteoclast actin cytoskeleton and bone resorption.
Article in BMC cell biology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 32 citations in OpenAlex.
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- L-Plastin Phosphorylation: Possible Regulation by a TNFR1 Signaling Cascade in Osteoclasts.Cells · 2021Article
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- Nm23-h1 binds to gelsolin and inactivates its actin-severing capacity to promote tumor cell motility and metastasis.Cancer research · 2013Article
- Type I phosphotidylinosotol 4-phosphate 5-kinase γ regulates osteoclasts in a bifunctional manner.The Journal of biological chemistry · 2013Article
- RNA therapeutics targeting osteoclast-mediated excessive bone resorption.Advanced drug delivery reviews · 2012Review
- Phosphatidylinositol 4,5-bisphosphate and PIP5-kinase Ialpha are required for invadopodia formation in human breast cancer cells.Cancer science · 2010Article
- Invadopodia and matrix degradation, a new property of prostate cancer cells during migration and invasion.The Journal of biological chemistry · 2008Article
- Dramatic inhibition of osteoclast sealing ring formation and bone resorption in vitro by a WASP-peptide containing pTyr294 amino acid.Journal of molecular signaling · 2008Article
- Podosomes and Invadopodia: Related structures with Common Protein Components that May Promote Breast Cancer Cellular Invasion.Breast cancer : basic and clinical research · 2008Article
- "Actin"g on GLUT4: membrane & cytoskeletal components of insulin action.Current diabetes reviews · 2007Review
- Identification of novel RANK polymorphisms and their putative association with low BMD among postmenopausal women.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2007Article
- Interactions between vacuolar H+-ATPases and microfilaments in osteoclasts.Journal of bioenergetics and biomembranes · 2005Review
- Hela l-CaD is implicated in the migration of endothelial cells/endothelial progenitor cells in human neoplasms.Cell adhesion & migrationArticle
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundGelsolin, an actin capping protein of osteoclast podosomes, has a unique function in regulating assembly and disassembly of the podosome actin filament. Previously, we have reported that osteopontin (OPN) binding to integrin alphavbeta3 increased the levels of gelsolin-associated polyphosphoinositides, podosome assembly/disassembly, and actin filament formation. The present study was undertaken to identify the possible role of polyphosphoinositides and phosphoinositides binding domains (PBDs) of gelsolin in the osteoclast cytoskeletal structural organization and osteoclast function.
resultsTransduction of TAT/full-length gelsolin and PBDs containing gelsolin peptides into osteoclasts demonstrated: 1) F-actin enriched patches; 2) disruption of actin ring; 3) an increase in the association polyphosphoinositides (PPIs) with the transduced peptides containing PBDs. The above-mentioned effects were more pronounced with gelsolin peptide containing 2 tandem repeats of PBDs (PBD (2)). Binding of PPIs to the transduced peptides has resulted in reduced levels of PPIs association with the endogenous gelsolin, and thereby disrupted the actin remodeling processes in terms of podosome organization in the clear zone area and actin ring formation. These peptides also exhibited a dominant negative effect in the formation of WASP-Arp2/3 complex indicating the role of phosphoinositides in WASP activation. The TAT-PBD gelsolin peptides transduced osteoclasts are functionally defective in terms of motility and bone resorption.
conclusionsTaken together, these data demonstrate that transduction of PBD gelsolin peptides into osteoclasts produced a dominant negative effect on actin assembly, motility, and bone resorption. These findings indicate that phosphoinositide-mediated signaling mechanisms regulate osteoclast cytoskeleton, podosome assembly/disassembly, actin ring formation and bone resorption activity of osteoclasts.
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