Microtubule Dynamic Instability Controls Podosome Patterning in Osteoclasts through EB1, Cortactin, and Src
Microtubule Dynamic Instability Controls Podosome Patterning in Osteoclasts through EB1, Cortactin, and Src
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DOI：
10.1128/mcb.00578-13
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发表时间：
2014-01-01
影响因子：
5.3
通讯作者：
Baron, Roland
中科院分区：
文献类型：
--
作者：
Duplan, Martin Biosse;Zalli, Detina;Baron, Roland
在破骨细胞（OCs）中，足小体呈带状组织，这是骨吸收的关键特征。虽然微管（MT）促进了带的形成和稳定性，但介导这两个系统相互作用的MT和/或podosome分子尚未被确定。由于MTs生长的“正”端指向足小体带，正端跟踪蛋白（+ TIPs）可能调节足小体的模式。在+ TIPs中，EB1随着OCs的成熟而增加，并在足小体带富集，EB1阳性的MTs靶向足小体。MT动态不稳定的抑制、MT末端EB1的移位或EB1的耗竭导致了podosome带的损失。我们确定了联系蛋白是EB1依赖src的相互作用伙伴。皮质蛋白缺乏的OCs表现为靶向足小体的MT缺陷和骨吸收减少。抑制MT动态不稳定性或EB1耗竭会增加接触蛋白磷酸化，降低其乙酰化并影响其与EB1的相互作用。因此，动态mt和足质体相互作用来控制骨吸收。
In osteoclasts (OCs) podosomes are organized in a belt, a feature critical for bone resorption. Although microtubules (MTs) promote the formation and stability of the belt, the MT and/or podosome molecules that mediate the interaction of the two systems are not identified. Because the growing "plus" ends of MTs point toward the podosome belt, plus-end tracking proteins (+ TIPs) might regulate podosome patterning. Among the + TIPs, EB1 increased as OCs matured and was enriched in the podosome belt, and EB1-positive MTs targeted podosomes. Suppression of MT dynamic instability, displacement of EB1 from MT ends, or EB1 depletion resulted in the loss of the podosome belt. We identified cortactin as an Src-dependent interacting partner of EB1. Cortactin- deficient OCs presented a defective MT targeting to, and patterning of, podosomes and reduced bone resorption. Suppression of MT dynamic instability or EB1 depletion increased cortactin phosphorylation, decreasing its acetylation and affecting its interaction with EB1. Thus, dynamic MTs and podosomes interact to control bone resorption.