Regulation of vacuolar H(+)-ATPase in microglia by RANKL.
Regulation of vacuolar H(+)-ATPase in microglia by RANKL.
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DOI：
10.1016/j.bbrc.2009.08.122
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发表时间：
2009-11-06
影响因子：
3.1
通讯作者：
Holliday, L. Shannon
中科院分区：
文献类型：
--
作者：
Serrano, Eric M.;Ricofort, Ryan D.;Zuo, Jian;Ochotny, Noelle;Manolson, Morris F.;Holliday, L. Shannon
关键词：
液泡H+-ATPase(V-ATPase)是由许多亚单位组成的大型生电质子泵，在内吞途径的隔室酸化中起着至关重要的管家作用。此外，V-ATPase在某些细胞类型中发挥着特殊的作用，这种能力与某些亚基的亚型的细胞类型选择性表达有关。我们在小鼠脑提取液中检测到低水平的a-亚单位的A3亚型。免疫印迹法检测各种脑源性细胞类型，发现A3在N9小胶质细胞系和原代小胶质细胞中表达，但在其他类型的细胞中不表达。破骨细胞中A3的表达需要核因子受体激活剂κB配体的刺激。我们发现核因子受体激活剂κB(RANK)在小胶质细胞中表达。RANKL刺激小胶质细胞后，A3表达增加。小胶质细胞中的V-ATPase与微丝结合，RANKL刺激后，V-ATPase与不溶于洗涤剂的细胞骨架部分和肌动蛋白的比例增加。综上所述，小胶质细胞表达V-ATPase的A3亚单位。RANKL对A3的表达及V-ATPase与微丝的相互作用均有调节作用。这些数据表明了一种新的调节小胶质细胞的分子途径。
Vacuolar H+-ATPases (V-ATPases) are large electrogenic proton pumps composed of numerous subunits that play vital housekeeping roles in the acidification of compartments of the endocytic pathway. Additionally, V-ATPase play specialized roles in certain cell types, a capacity that is linked to cell type selective expression of isoforms of some of the subunits. We detected low levels of the a3 isoform of the a-subunit in mouse brain extracts. Examination of various brain-derived cell types by immunoblotting showed a3 was expressed in the N9 microglia cell line and in primary microglia, but not in other cell types. The expression of a3 in osteoclasts requires stimulation by Receptor Activator of Nuclear Factor κ B -ligand (RANKL). We found that Receptor Activator of Nuclear Factor κ B (RANK) was expressed by microglia. Stimulation of microglia with RANKL triggered increased expression of a3. V-ATPases in microglia were shown to bind microfilaments, and stimulation with RANKL increased the proportion of V-ATPase associated with the detergent-insoluble cytoskeletal fraction and with actin. In summary, microglia express the a3-subunit of V-ATPase. The expression of a3 and the interaction between V-ATPases and microfilaments was modulated by RANKL. These data suggest a novel molecular pathway for regulating microglia.
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影响因子：
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作者：
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通讯作者：
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