Dynamic changes in the osteoclast cytoskeleton in response to growth factors and cell attachment are controlled by beta3 integrin.
Dynamic changes in the osteoclast cytoskeleton in response to growth factors and cell attachment are controlled by beta3 integrin.
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DOI：
10.1083/jcb.200212082
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发表时间：
2003-08-04
期刊：
影响因子：
--
通讯作者：
Teitelbaum SL
中科院分区：
文献类型：
--
作者：
Faccio R;Novack DV;Zallone A;Ross FP;Teitelbaum SL
β3整合素胞浆结构域，特别是S752，对整合素定位和破骨细胞(OC)功能至关重要。由于巨噬细胞集落刺激因子和肝细胞生长因子等生长因子通过内向外信号影响整合素的激活和功能，这一过程需要β整合素胞浆尾巴，因此我们检测了这些生长因子对OC前体的影响。为此，我们逆转录病毒表达了不同的β-3整合素，并在β-3缺失的OC前体细胞中进行了胞质尾部突变。我们发现，β3胞浆尾部的S752是生长因子诱导的整合素激活、细胞骨架重组和膜突起所必需的，从而影响OC的黏附、迁移和骨吸收。β3亚基缺失的OC前体细胞中，Rho和Rac两种小分子GTP酶参与细胞骨架的重组，而Rho和Rac的激活缺陷。上游调节因子c-Src和c-Cb1的激活也依赖于β3。有趣的是，尽管β相关的激酶PYK2与c-Src和c-Cb1相互作用，但它的激活不会在缺乏功能性β3的情况下中断。相反，它的激活依赖于细胞内钙离子和β2整合素。因此，β3胞质结构域负责激活特定的细胞内信号，导致对OC功能至关重要的细胞骨架重组。
The β3 integrin cytoplasmic domain, and specifically S752, is critical for integrin localization and osteoclast (OC) function. Because growth factors such as macrophage colony–stimulating factor and hepatocyte growth factor affect integrin activation and function via inside-out signaling, a process requiring the β integrin cytoplasmic tail, we examined the effect of these growth factors on OC precursors. To this end, we retrovirally expressed various β3 integrins with cytoplasmic tail mutations in β3-deficient OC precursors. We find that S752 in the β3 cytoplasmic tail is required for growth factor–induced integrin activation, cytoskeletal reorganization, and membrane protrusion, thereby affecting OC adhesion, migration, and bone resorption. The small GTPases Rho and Rac mediate cytoskeletal reorganization, and activation of each is defective in OC precursors lacking a functional β3 subunit. Activation of the upstream mediators c-Src and c-Cbl is also dependent on β3. Interestingly, although the FAK-related kinase Pyk2 interacts with c-Src and c-Cbl, its activation is not disrupted in the absence of functional β3. Instead, its activation is dependent upon intracellular calcium, and on the β2 integrin. Thus, the β3 cytoplasmic domain is responsible for activation of specific intracellular signals leading to cytoskeletal reorganization critical for OC function.
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影响因子：
4.8
作者：
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通讯作者：
Hruska, KA
影响因子：
56.9
作者：
Cukierman, E;Pankov, R;Yamada, KM
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影响因子：
3.3
作者：
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通讯作者：
Blystone, S
影响因子：
15.9
作者：
Engelman, VW;Nickols, GA;Teitelbaum, SL
通讯作者：
Teitelbaum, SL
DOI：
10.1083/jcb.152.2.361
发表时间：
2001-01-22
期刊：
The Journal of cell biology
影响因子：
--
作者：
Nakamura I;Lipfert L;Rodan GA;Le T Duong
通讯作者：
Le T Duong