Aquaporin 3 colocates with phospholipase D2 in caveolin-rich membrane microdomains and is downregulated upon keratinocyte differentiation

[摘要] 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.

[发布日期] 2003-12-01

[关键词] aquaporin;keratinocytes;lipid rafts;phosphatidylglycerol;phospholipase D