Septins are critical regulators of osteoclastic bone resorption.
Anaïs Marie Julie Møller,Ernst-Martin Füchtbauer,Annemarie Brüel,Thomas Levin Andersen,Xenia G. Borggaard,Nathan J. Pavlos,Jesper Skovhus Thomsen,Finn Skou Pedersen,Jean-Marie Delaissé,Kent Søe +9 more
TL;DR: This work shows that the SEPT9 gene and Septin 9 (SEPT9) protein are expressed and synthesized during differentiation of human osteoclasts and suggests a role for septins in bone resorption.
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Abstract: Septins are known to play key roles in supporting cytoskeletal stability, vesicular transport, endo-/exocytosis, stabilizing cellular membranes and forming diffusion barriers. Their function in mammalian cells is poorly investigated. The osteoclast offers an interesting tool to investigate septins because all cellular activities septins were reported to be involved in are critical for osteoclasts. However, the existence of septins in osteoclasts has not even been reported. Here we show that the SEPT9 gene and Septin 9 (SEPT9) protein are expressed and synthesized during differentiation of human osteoclasts. Pharmacological stabilization of septin filaments dose dependently inhibits bone resorption of human osteoclasts in vitro suggesting a role for septins in bone resorption. Attesting to this, conditional deletion of Sept9 in mice leads to elevated levels of trabecular bone and diminished femoral growth in vivo. Finally, systematic interrogation of the spatial organization of SEPT9 by confocal microscopy reveals that SEPT9 is closely associated to the structures known to be critical for osteoclast activity. We propose that septins in general and SEPT9 in particular play a previously unappreciated role in osteoclastic bone resorption.
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TL;DR: It is underscored that fully understanding the control of bone resorption requires to consider it in both space and time - which demands taking into account the context of bone tissue.
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Osteoclasts' Ability to Generate Trenches Rather Than Pits Depends on High Levels of Active Cathepsin K and Efficient Clearance of Resorption Products.
TL;DR: It is shown that a mechanism integrating release of resorption products and membrane/integrin recycling is required for prolongation of trench mode, which contributes to an improved understanding of the molecular and cellular determinants for the two osteoclastic bone resOrption modes.
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Septins as membrane influencers: direct play or in association with other cytoskeleton partners
TL;DR: In this article , the authors report recent works that address how septins bind to membranes, and influence their shaping, organization, properties and functions, either by binding to them directly or indirectly through other cytoskeleton elements.
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Self- and Actin-Templated Assembly of Mammalian Septins
Makoto Kinoshita,Christine M. Field,Margaret Coughlin,Aaron F. Straight,Timothy J. Mitchison +4 more
TL;DR: It is concluded that septin alone self-assemble into rings, that adaptor proteins recruit septins to actin bundles, and that sePTins help organize these bundles.
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A Septin Diffusion Barrier at the Base of the Primary Cilium Maintains Ciliary Membrane Protein Distribution
Qicong Hu,Ljiljana Milenkovic,Ljiljana Milenkovic,Hua Jin,Matthew P. Scott,Maxence V. Nachury,Elias T. Spiliotis,W. James Nelson +7 more
TL;DR: Septin 2 (SEPT2), a member of the septin family of guanosine triphosphatases that form a diffusion barrier in budding yeast, localized at the base of the ciliary membrane and is essential for retaining receptor-signaling pathways in the primary cilium.