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Nanoscale architecture and coordination of actin cores within the sealing zone of human osteoclasts

Marion Portes, Thomas Mangeat, Natacha Escallier, View ORCID ProfileBrigitte Raynaud-Messina, Christophe Thibault, Isabelle Maridonneau-Parini, View ORCID ProfileChristel Vérollet, View ORCID ProfileRenaud Poincloux
doi: https://doi.org/10.1101/2021.12.09.471901
Marion Portes
1Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, France
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Thomas Mangeat
2LBCMCP, Centre de Biologie Intégrative, Université de Toulouse, CNRS, UPS, France
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Natacha Escallier
1Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, France
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Brigitte Raynaud-Messina
1Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, France
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  • ORCID record for Brigitte Raynaud-Messina
Christophe Thibault
3LAAS-CNRS, Université de Toulouse, CNRS, INSA, Toulouse, France
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  • For correspondence: christophe.thibault@laas.fr christel.verollet@ipbs.fr renaud.poincloux@ipbs.fr
Isabelle Maridonneau-Parini
1Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, France
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Christel Vérollet
1Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, France
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  • ORCID record for Christel Vérollet
  • For correspondence: christophe.thibault@laas.fr christel.verollet@ipbs.fr renaud.poincloux@ipbs.fr
Renaud Poincloux
1Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, France
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  • ORCID record for Renaud Poincloux
  • For correspondence: christophe.thibault@laas.fr christel.verollet@ipbs.fr renaud.poincloux@ipbs.fr
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Abstract

Osteoclasts are unique in their capacity to degrade bone tissue. To achieve this process, osteoclasts form a specific structure called the sealing zone, which creates a close contact with bone and confines the release of protons and hydrolases for bone degradation. The sealing zone is composed of actin structures called podosomes nested in a dense actin network. The organization of these actin structures inside the sealing zone at the nano scale is still unknown. Here, we combine cutting-edge microscopy methods to reveal the nanoscale architecture and dynamics of the sealing zone formed by human osteoclasts on bone surface. Random illumination microscopy allowed the identification and live imaging of densely packed actin cores within the sealing zone. A cross-correlation analysis of the fluctuations of actin content at these cores indicates that they are locally synchronized. Further examination shows that the sealing zone is composed of groups of synchronized cores linked by α-actinin1 positive filaments, and encircled by adhesion complexes. Thus, we propose that the confinement of bone degradation mediators is achieved through the coordination of islets of actin cores and not by the global coordination of all podosomal subunits forming the sealing zone.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted December 11, 2021.
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Nanoscale architecture and coordination of actin cores within the sealing zone of human osteoclasts
Marion Portes, Thomas Mangeat, Natacha Escallier, Brigitte Raynaud-Messina, Christophe Thibault, Isabelle Maridonneau-Parini, Christel Vérollet, Renaud Poincloux
bioRxiv 2021.12.09.471901; doi: https://doi.org/10.1101/2021.12.09.471901
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Nanoscale architecture and coordination of actin cores within the sealing zone of human osteoclasts
Marion Portes, Thomas Mangeat, Natacha Escallier, Brigitte Raynaud-Messina, Christophe Thibault, Isabelle Maridonneau-Parini, Christel Vérollet, Renaud Poincloux
bioRxiv 2021.12.09.471901; doi: https://doi.org/10.1101/2021.12.09.471901

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