Biology subjects

Verdys, P.

Publications and source records attributed to Verdys, P..

3 recordsLinked to original sources

bioRxiv2025

Myo1e/f at the podosome base regulate podosome dynamics and promote macrophage migration

Cells of the monocyte lineage form specialized membrane-associated, actin-rich structures, called podosomes. Podosomes play important roles in cell adhesion and migration as well as the proteolytic degradation of the extracellular matrix. While podosomes are always closely associated with the plasma membrane, the structural components linking the podosome core, composed of branched actin, to the membrane are not fully understood. In this study we show that class I myosins, Myo1e and Myo1f, localize to a specific region of podosomes, underneath the podosome core and near the ventral plasma membrane, and that this localization is mainly mediated by the Myo1e/f TH2 domains. Respective knockdowns or knockouts of Myo1e/f lead to increased podosome size, altered turnover and lateral mobility, which is likely due to Myo1e/f regulating the attachment of core actin filaments to the plasma membrane. In addition, Myo1e/f double knockout macrophages were characterized by a reduction in 3D and 2D migration, even though these cells exhibited increased ability to degrade the extracellular matrix. Along with the other membrane-associated podosome components, such as the transmembrane proteins MT-MMP and CD44, and the GPI-anchored DNase X, Myo1e and Myo1f mark the membrane-proximal region of podosomes. We propose to label this region as the podosome "base", an additional substructure joining the current trifecta of the podosome cap, core, and ring.

cell biology↗

bioRxiv2024

Moesin activation controls bone resorption and tunneling nanotube-dependent osteoclast fusion

Cell-cell fusion is an evolutionarily conserved process that is essential for many functions, including fertilisation and the formation of placenta, muscle and osteoclasts, multinucleated cells that are unique in their ability to resorb bone. The mechanisms of osteoclast multinucleation involve dynamic interactions between the actin cytoskeleton and the plasma membrane that are still poorly characterized. Here, we found that moesin, a cytoskeletal linker protein member of the Ezrin/Radixin/Moesin (ERM) protein family, is activated during osteoclast maturation and plays an instrumental role in both osteoclast fusion and function. In mouse and human osteoclast precursors, moesin inhibition favors their ability to fuse into multinucleated osteoclasts. Accordingly, we demonstrated that moesin depletion decreases membrane-to-cortex attachment and enhances the formation of tunneling nanotubes (TNTs), F-actin-based intercellular bridges that we reveal here to trigger cell-cell fusion. Moesin also controls HIV-1- and inflammation-induced cell fusion. In addition, moesin regulates the formation of the sealing zone, the adhesive structure determining osteoclast bone resorption area, and thus controls bone degradation, via a {beta}3-integrin/RhoA/SLK pathway. Supporting our results, moesin-deficient mice present a reduced density of trabecular bones and increased osteoclast abundance and activity. These findings provide a better understanding of the regulation of cell-cell fusion and osteoclast biology, opening new opportunities to specifically target osteoclast activity in bone disease therapy.

cell biology↗

bioRxiv2023

The membrane-actin linkers ezrin, radixin, and moesin are dispensable for macrophage migration and cortex mechanics.

The cellular actin cortex provides crucial mechanical support and plays critical roles in numerous functions, including cell division and migration. The proteins of the ERM family, ezrin, radixin, and moesin, are central to these processes by linking the plasma membrane to the actin cytoskeleton. To investigate the individual contributions of these three proteins to leukocyte migration, we generated single and triple ERM knock-out macrophages. Surprisingly, we found that even in the absence of ERMs, macrophages can still form the different actin structures promoting cell migration, such as filopodia, lamellipodia, podosomes, and ruffles. Furthermore we discovered that, unlike every other cell type previously investigated, the single or triple knock-out of ERMs does not affect macrophage migration in a large diversity of contexts. Finally, we demonstrated that the loss of ERMs in macrophages does not affect the mechanics of their actin cortex. These findings challenge the notion that ERMs are universally essential for cortex mechanics and cell migration and support the notion that the macrophage cortex may have diverged from that of other cells to allow for their adaptive cortical plasticity.

cell biology↗