PT  - JOURNAL ARTICLE
AU  - Marion Portes
AU  - Thomas Mangeat
AU  - Natacha Escallier
AU  - Brigitte Raynaud-Messina
AU  - Christophe Thibault
AU  - Isabelle Maridonneau-Parini
AU  - Christel Vérollet
AU  - Renaud Poincloux
TI  - Nanoscale architecture and coordination of actin cores within the sealing zone of human osteoclasts
AID  - 10.1101/2021.12.09.471901
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.12.09.471901
4099  - http://biorxiv.org/content/early/2021/12/11/2021.12.09.471901.short
4100  - http://biorxiv.org/content/early/2021/12/11/2021.12.09.471901.full
AB  - 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 StatementThe authors have declared no competing interest.