Intracellular membrane trafficking in bone resorbing osteoclasts
Intracellular membrane trafficking in bone resorbing osteoclasts
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DOI：
10.1002/jemt.10371
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发表时间：
2003-08-15
影响因子：
2.5
通讯作者：
Väänänen, HK
中科院分区：
文献类型：
--
作者：
Mulari, M;Vääräniemi, J;Väänänen, HK
现在有充分的证据表明骨吸收中的两个主要事件，即羟基磷灰石的溶解和有机基质的降解，是由破骨细胞执行的。吸收周期涉及几种特定的细胞活动，其中细胞内囊泡运输起着至关重要的作用。尽管这些过程的细节直到最近才开始公开，但很明显，破骨细胞功能的几个具体步骤需要囊泡运输。在吸收细胞的极化过程中形成了几个质膜域。多核破骨细胞与细胞外基质形成紧密密封，作为其吸收活性的第一个指标。密封区形成的初始步骤是α(v)β(3)-整合素介导的，但质膜和矿化骨基质之间的最终分子相互作用仍然未知。然后大量酸性细胞内囊泡与面向骨的质膜融合，形成褶皱边界膜，这是真正的重吸收细胞器。褶皱边界的形成是由一种小的 GTP 结合蛋白 rab7 调节的，它表明了褶皱边界膜的晚期内体特征。破骨细胞中特定膜运输过程的细节，例如密封区的形成和骨降解产物从吸收腔到功能性分泌域的转胞吞作用仍有待澄清。人们很容易推测囊泡运输的具体特征可能为骨疾病的药物治疗提供几个潜在的新靶点。 (C) 2003 Wiley-Liss, Inc.
There is ample evidence now that the two major events in bone resorption, namely dissolution of hydroxyapatite and degradation of the organic matrix, are performed by osteoclasts. The resorption cycle involves several specific cellular activities, where intracellular vesicular trafficking plays a crucial role. Although details of these processes started to open up only recently, it is clear that vesicular trafficking is needed in several specific steps of osteoclast functioning. Several plasma membrane domains are formed during the polarization of the resorbing cells. Multinucleated osteoclasts create a tight sealing to the extracellular matrix as a first indicator of their resorption activity. Initial steps of the sealing zone formation are alpha(v)beta(3)-integrin mediated, but the final molecular interaction(s) between the plasma membrane and mineralized bone matrix is still unknown. A large number of acidic intracellular vesicles then fuse with the bone-facing plasma membrane to form a ruffled border membrane, which is the actual resorbing organelle. The formation of a ruffled border is regulated by a small GTP-binding protein, rab7, which indicates the late endosomal character of the ruffled border membrane. Details of specific membrane transport processes in the osteoclasts, e.g., the formation of the sealing zone and transcytosis of bone degradation products from the resorption lacuna to the functional secretory domain remain to be clarified. It is tempting to speculate that specific features of vesicular trafficking may offer several potential new targets for drug therapy of bone diseases. (C) 2003 Wiley-Liss, Inc.