Microtubule Dynamic Instability Controls Podosome Patterning in Osteoclasts through EB1, Cortactin, and Src
| Autor: | Klemens Rottner, Frank P. L. Lai, Roland Baron, Detina Zalli, Lynn Neff, Sebastien Robert Stephens, Martin Biosse Duplan, William C. Horne, J. Margit Oelkers, Serhan Zenger |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Podosome
Microtubule-associated protein Green Fluorescent Proteins Immunoblotting Gene Expression Osteoclasts macromolecular substances Biology Cell Membrane Structures Microtubules Bone resorption Cell Line Mice Microtubule Animals Humans Phosphorylation Molecular Biology Actin Cells Cultured Genetics Mice Knockout Microscopy Confocal Reverse Transcriptase Polymerase Chain Reaction fungi Acetylation Cell Biology Articles Actins Cell biology Kinetics HEK293 Cells src-Family Kinases biology.protein RNA Interference Cortactin Microtubule-Associated Proteins Proto-oncogene tyrosine-protein kinase Src Protein Binding |
| Popis: | In osteoclasts (OCs) podosomes are organized in a belt, a feature critical for bone resorption. Although microtubules (MTs) promote the formation and stability of the belt, the MT and/or podosome molecules that mediate the interaction of the two systems are not identified. Because the growing "plus" ends of MTs point toward the podosome belt, plus-end tracking proteins (+TIPs) might regulate podosome patterning. Among the +TIPs, EB1 increased as OCs matured and was enriched in the podosome belt, and EB1-positive MTs targeted podosomes. Suppression of MT dynamic instability, displacement of EB1 from MT ends, or EB1 depletion resulted in the loss of the podosome belt. We identified cortactin as an Src-dependent interacting partner of EB1. Cortactin-deficient OCs presented a defective MT targeting to, and patterning of, podosomes and reduced bone resorption. Suppression of MT dynamic instability or EB1 depletion increased cortactin phosphorylation, decreasing its acetylation and affecting its interaction with EB1. Thus, dynamic MTs and podosomes interact to control bone resorption. |
| Databáze: | OpenAIRE |
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