The kinesin KIF9 and reggie/flotillin proteins regulate matrix degradation by macrophage podosomes.
The kinesin KIF9 and reggie/flotillin proteins regulate matrix degradation by macrophage podosomes.
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DOI：
10.1091/mbc.e10-05-0394
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发表时间：
2011-01-15
影响因子：
3.3
通讯作者：
Linder S
中科院分区：
文献类型：
--
作者：
Cornfine S;Himmel M;Kopp P;El Azzouzi K;Wiesner C;Krüger M;Rudel T;Linder S
在多种细胞类型中，足状体是基于肌动蛋白的基质接触。这项研究确定了驱动蛋白KIF 9和reggie/flotillin蛋白作为巨噬细胞podosomes的新型调节剂，并表明它们通过KIF 9独特的C-末端结构域的相互作用对这些结构的基质降解能力至关重要。在多种细胞类型中，最显著的是单核细胞，足体是基于肌动蛋白的基质接触，并且其特征在于其裂解细胞外基质材料的能力。除了依赖于肌动蛋白的调节外，podosomes还受到微管和微管依赖性运输过程的影响。在这里，我们描述了一个新的作用KIF 9，以前很少表征的驱动蛋白运动家族的成员，在原代人类巨噬细胞的调节的podosomes。我们发现，小干扰RNA（siRNA）/短发夹RNA诱导的KIF 9敲低显着影响的数量和基质降解的podosomes。过表达和显微注射实验表明，KIF 9独特的C-末端区域对这些效应至关重要，可能是通过结合特定的相互作用。事实上，我们进一步确定reggie-1/flotillin-2，细胞内囊泡和细胞周边之间的信号传导介质，作为KIF 9 C-末端的相互作用。Reggie-1在活细胞中与KIF 9动态共定位，并且与KIF 9介导的作用一致，siRNA诱导的reggies/flotillin的敲低显著损害了由podosomes引起的基质降解。总之，我们确定了驱动蛋白KIF 9和雷吉/flotillin蛋白作为巨噬细胞podosomes的新的调节剂，并表明它们的相互作用是这些结构的基质降解能力的关键。
Podosomes are actin-based matrix contacts in a variety of cell types. This study identifies the kinesin KIF9 and reggie/flotillin proteins as novel regulators of macrophage podosomes and shows that their interaction through the unique C-terminal domain of KIF9 is critical for the matrix-degrading ability of these structures. Podosomes are actin-based matrix contacts in a variety of cell types, most notably monocytic cells, and are characterized by their ability to lyse extracellular matrix material. Besides their dependence on actin regulation, podosomes are also influenced by microtubules and microtubule-dependent transport processes. Here we describe a novel role for KIF9, a previously little-characterized member of the kinesin motor family, in the regulation of podosomes in primary human macrophages. We find that small interfering RNA (siRNA)/short-hairpin RNA–induced knockdown of KIF9 significantly affects both numbers and matrix degradation of podosomes. Overexpression and microinjection experiments reveal that the unique C-terminal region of KIF9 is crucial for these effects, presumably through binding of specific interactors. Indeed, we further identify reggie-1/flotillin-2, a signaling mediator between intracellular vesicles and the cell periphery, as an interactor of the KIF9 C-terminus. Reggie-1 dynamically colocalizes with KIF9 in living cells, and, consistent with KIF9-mediated effects, siRNA-induced knockdown of reggies/flotillins significantly impairs matrix degradation by podosomes. In sum, we identify the kinesin KIF9 and reggie/flotillin proteins as novel regulators of macrophage podosomes and show that their interaction is critical for the matrix-degrading ability of these structures.