The Actin-Binding Protein Cofilin and Its Interaction With Cortactin Are Required for Podosome Patterning in Osteoclasts and Bone Resorption In Vivo and In Vitro.
The Actin-Binding Protein Cofilin and Its Interaction With Cortactin Are Required for Podosome Patterning in Osteoclasts and Bone Resorption In Vivo and In Vitro.
复制标题
DOI：
10.1002/jbmr.2851
复制
发表时间：
2016-09
影响因子：
6.2
通讯作者：
Baron, Roland
中科院分区：
文献类型：
--
作者：
Zalli, Detina;Neff, Lynn;Nagano, Kenichi;Shin, Nah Young;Witke, Walter;Gori, Francesca;Baron, Roland
破骨细胞（OCs）与骨的粘附和骨吸收需要特定的F-肌动蛋白粘附结构、足状体的组装以及它们在密封区中的致密包装。密封区的OC特异性形成需要微管（MT）+末端与podosomes的相互作用。在这里，我们删除了cofilin（一种在OC中高度表达的皮质蛋白（CTTN）和肌动蛋白结合蛋白），以确定它是否作用于MT-CTTN轴下游来调节足粒中的肌动蛋白聚合。组织蛋白酶K启动子（Ctsk-Cre）驱动的小鼠OC中cofilin的条件性缺失，损害体内骨吸收，增加骨密度。在体外，OC不能将podosomes组织成外周带。MT网络紊乱，MT稳定性降低，细胞迁移受损。活性cofilin稳定MT并允许足体带形成，而MT破坏通过磷酸化使cofilin失活。Cofilin与CTTN相互作用的podosomes和磷酸化的蛋白质破坏这种相互作用，这是关键的带稳定和MT动态不稳定的维护。因此，需要活性cofilin在体外拯救OC细胞骨架表型。这些发现表明，进入密封区的podosomes的图案涉及cofilin，CTTN和MT加端之间的动态相互作用。这种相互作用对于OC的功能组织和骨吸收至关重要。关键词：Cofilin，破骨细胞，骨，Podosome，肌动蛋白
The adhesion of osteoclasts (OCs) to bone and bone resorption require the assembly of specific F-actin adhesion structures, the podosomes, and their dense packing into a sealing zone. The OC-specific formation of the sealing zone requires the interaction of microtubule (MT) + ends with podosomes. Here we deleted cofilin, a cortactin (CTTN)- and actin-binding protein highly expressed in OCs, to determine if it acts downstream of the MT-CTTN axis to regulate actin polymerization in podosomes. Conditional deletion of cofilin in OCs in mice, driven by the cathepsin K promoter (Ctsk-Cre), impaired bone resorption in vivo, increasing bone density. In vitro, OCs were not able to organize podosomes into peripheral belts. The MT network was disorganized, MT stability was decreased and cell migration impaired. Active cofilin stabilizes MTs and allows podosome belt formation, whereas MT disruption de-activates cofilin via phosphorylation. Cofilin interacts with CTTN in podosomes and phosphorylation of either protein disrupts this interaction, which is critical for belt stabilization and for the maintenance of MT dynamic instability. Accordingly, active cofilin was required to rescue the OC cytoskeletal phenotype in vitro. These findings suggest that the patterning of podosomes into a sealing zone involves the dynamic interaction between cofilin, CTTN and the MTs plus-ends. This interaction is critical for the functional organization of OCs and for bone resorption. Key Words: Cofilin, Osteoclast, Bone, Podosome, Actin
登录
查看更多内容
影响因子：
4
作者：
Luxenburg, Chen;Parsons, J. Thomas;Geiger, Benjamin
通讯作者：
Geiger, Benjamin
影响因子：
5.3
作者：
Duplan, Martin Biosse;Zalli, Detina;Baron, Roland
通讯作者：
Baron, Roland
影响因子：
3.3
作者：
Destaing, O;Saltel, F;Bard, F
通讯作者：
Bard, F
影响因子：
6.6
作者：
Jurdic, P;Saltel, F;Destaing, O
通讯作者：
Destaing, O
肌动蛋白去聚合因子（ADF/Cofilin）提高了细丝流动率：基于肌动蛋白的运动的影响。
DOI：
10.1083/jcb.136.6.1307
发表时间：
1997-03-24
期刊：
The Journal of cell biology
影响因子：
--
作者：
Carlier MF;Laurent V;Santolini J;Melki R;Didry D;Xia GX;Hong Y;Chua NH;Pantaloni D
通讯作者：
Pantaloni D