Cell biology of osteoclasts II: PSTP1, an adaptor of protein tyrosine phosphatases, as a major component controlling of actin and sealing zone dynamics during bone degradation

破骨细胞的细胞生物学 II：PSTP1，蛋白酪氨酸磷酸酶的接头，作为骨降解过程中控制肌动蛋白和密封区动力学的主要成分

• 批准号: 204054066
• 负责人: Professor Dr. Bernard Hoflack
• 金额: --
• 依托单位: Biotechnologisches Zentrum (Biotec)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2011
• 资助国家: 德国
• 起止时间: 2010-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/204054066?language=en
• 关键词: Cell; biology; osteoclasts; II; PSTP1

To digest bone, osteoclasts need to adhere onto its surface, to build up a sealing zone by reorganizing their actin-rich podosomes into tight belts. These events are controlled by the Src tyrosine kinase, Using quantitative proteomics, we have previously identified the proline-serine-threonine phosphataseinteracting protein 1 (PSTPIP1) as a Src substrate. Our working hypothesis is that PSTPIP1 binds to podosomes via its F-BAR domain where it recruits via its SH3 domain PEST-protein tyrosine phosphatases, which could then inactivate key components of podosomes thereby destabilizing sealing zones. To comprehensively understand PSTPIP1 function in osteoclasts, it will be necessary 1. To understand how PSTPIP1 is recruited onto podosomes and how its activity is regulated, 2. To identify its interacting partners, in particular specific protein tyrosine phosphatases and 3. To identify the substrates of these phosphatases, which are likely key structural and regulatory components of sealing zone dynamics. The project will combine quantitative proteomic analyses and functional studies based on videomicroscopy applied to siRNA treated osteoclasts.

为了消化骨骼，破骨细胞需要粘附在其表面，通过将其富含肌动蛋白的podosome重组成紧密的带来建立密封区。这些事件是由Src酪氨酸激酶控制的，使用定量蛋白质组学，我们以前已经确定了脯氨酸-丝氨酸-苏氨酸磷酸酶相互作用蛋白1（PSTPIP 1）作为Src底物。我们的工作假设是PSTPIP 1通过其F-BAR结构域与足体结合，在那里它通过其SH 3结构域招募PEST蛋白酪氨酸磷酸酶，然后可以破坏足体的关键组分，从而使密封区不稳定。为了全面了解PSTPIP 1在破骨细胞中的功能，有必要1。为了了解PSTPIP 1是如何被募集到podosomes上以及其活性是如何被调节的，2。为了确定其相互作用的伙伴，特别是特定的蛋白酪氨酸磷酸酶和3。确定这些磷酸酶的底物，这些磷酸酶可能是密封区动力学的关键结构和调节成分。该项目将结合联合收割机定量蛋白质组学分析和基于应用于siRNA处理的破骨细胞的视频显微镜的功能研究。