Aquaporin 3 colocates with phospholipase D2 in caveolin-rich membrane microdomains and is downregulated upon keratinocyte differentiation
Aquaporin 3 colocates with phospholipase D2 in caveolin-rich membrane microdomains and is downregulated upon keratinocyte differentiation
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DOI：
10.1111/j.1523-1747.2003.12614.x
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发表时间：
2003-12-01
影响因子：
6.5
通讯作者：
Bollag, WB
中科院分区：
文献类型：
--
作者：
Zheng, XJ;Bollag, WB
水通道蛋白3是运输水和甘油的通道。水通道蛋白3缺乏小鼠表现出皮肤缺陷，包括甘油含量降低、持水能力、屏障恢复和伤口愈合受损。无论水通道蛋白3及其甘油运输能力是否参与调节角化细胞功能，我们之前已经证明磷脂酶D-2可以在甘油存在的情况下代谢磷脂以产生磷脂酰甘油。我们假设水通道蛋白3通过水通道蛋白3和磷脂酶d之间的相互作用参与角化细胞功能的调节。使用蔗糖梯度离心、免疫沉淀分析和共聚焦显微镜，我们发现水通道蛋白3和磷脂酶D-2共定位在富含小泡蛋白的膜微域。此外，水通道蛋白3的表达在转录水平上下调，甘油摄取在原代小鼠角质形成细胞分化时减少，以响应细胞外钙浓度升高或1,25-二羟基维生素D-3。我们的研究结果表明，水通道蛋白3和磷脂酶D-2在脂筏中形成一个信号模块，其中水通道蛋白3将甘油转运到磷脂酶D-2以合成磷脂酰甘油。磷脂酰甘油作为一种生物活性脂质，可能介导水通道蛋白3-磷脂酶D-2信号模块的作用，水通道蛋白3作为调节单元，在角化细胞功能的调节中起作用。
Aquaporin 3 is a channel that transports both water and glycerol. Aquaporin 3-deficient mice exhibit skin defects, including decreased glycerol content and impairment of water holding capacity, barrier recovery, and wound healing. Whether aquaporin 3 and its glycerol transporting capacity are involved in regulating keratinocyte function, we have previously shown that phospholipase D-2 can metabolize phospholipids in the presence of glycerol to yield phosphatidylglycerol. We hypothesized that aquaporin 3 is involved in the regulation of keratinocyte function by a mechanism involving the interaction between aquaporin 3 and phospholipase D. Using sucrose gradient centrifugation, immunoprecipitation analysis, and confocal microscopy, we found that aquaporin 3 and phospholipase D-2 colocalized in caveolin-rich membrane microdomains. In addition, aquaporin 3 expression was downregulated at the transcriptional level and glycerol uptake was reduced upon primary mouse keratinocytes to differentiation in response to an elevated extracellular calcium concentration or 1,25-dihydroxyvitamin D-3. Our results suggest that aquaporin 3 and phospholipase D-2 form a signaling module in lipid rafts, where aquaporin 3 transports glycerol to phospholipase D-2 for the synthesis of phosphatidylglycerol. Phosphatidylglycerol, as a bioactive lipid, could potentially mediate the effects of the aquaporin 3-phospholipase D-2 signaling module, with aquaporin 3 as a modulatory unit, in the regulation of keratinocyte function.