TY - JOUR
T1 - A potential role for the phospholipase D2-aquaporin-3 signaling module in early keratinocyte differentiation
T2 - Production of a phosphatidylglycerol signaling lipid
AU - Bollag, Wendy B.
AU - Xie, Ding
AU - Zheng, Xiangjian
AU - Zhong, Xiaofeng
N1 - Funding Information:
We acknowledge Dr Daniel Bikle (University of California, San Francisco, CA) for his kind gift of the involucrin promoter-luciferase reporter construct, Dr Bogi Andersen (University of California, Irvine, CA) for his generous contribution of the keratin 5- and keratin 10-promoter-luciferase constructs and Dr Richard Eckert for his magnanimous provision of the anti-involucrin antibody. This work was supported in part by award no. AR45212 from the National Institutes of Health (National Institute of Arthritis and Musculoskeletal and Skin Diseases).
PY - 2007/12
Y1 - 2007/12
N2 - In keratinocytes aquaporin-3 (AQP3), an efficient glycerol transporter, is associated with phospholipase D2 (PLD2) in caveolin-rich membrane microdomains. PLD catalyzes both phospholipid hydrolysis to produce phosphatidate and a transphosphatidylation reaction using primary alcohols to generate phosphatidylalcohols. As PLD2 can utilize the physiological alcohol glycerol to form phosphatidylglycerol (PG), we hypothesized that AQP3 provides glycerol to PLD2 for PG synthesis, which then modulates keratinocyte function. Acidic medium inhibits AQP3 transport activity; both glycerol uptake and PG synthesis were inhibited by low versus physiological pH. Co-transfection experiments were performed in which AQP3 or empty vector was introduced into keratinocytes simultaneously with reporter constructs in which differentiation or proliferation promoters directed expression of a luciferase reporter gene. AQP3 coexpression decreased the promoter activity of keratin 5, increased that of keratin 10 and enhanced the effect of a differentiating agent on the promoter activity of involucrin, consistent with promotion of early differentiation. Glycerol inhibited DNA synthesis, whereas equivalent concentrations of xylitol or sorbitol, as osmotic controls, had no effect. Direct provision of PG, but not phosphatidylpropanol, inhibited DNA synthesis in proliferative cells. Thus, our results support the idea that AQP3 supplies PLD2 with glycerol for synthesizing PG, a lipid signal that promotes early keratinocyte differentiation.
AB - In keratinocytes aquaporin-3 (AQP3), an efficient glycerol transporter, is associated with phospholipase D2 (PLD2) in caveolin-rich membrane microdomains. PLD catalyzes both phospholipid hydrolysis to produce phosphatidate and a transphosphatidylation reaction using primary alcohols to generate phosphatidylalcohols. As PLD2 can utilize the physiological alcohol glycerol to form phosphatidylglycerol (PG), we hypothesized that AQP3 provides glycerol to PLD2 for PG synthesis, which then modulates keratinocyte function. Acidic medium inhibits AQP3 transport activity; both glycerol uptake and PG synthesis were inhibited by low versus physiological pH. Co-transfection experiments were performed in which AQP3 or empty vector was introduced into keratinocytes simultaneously with reporter constructs in which differentiation or proliferation promoters directed expression of a luciferase reporter gene. AQP3 coexpression decreased the promoter activity of keratin 5, increased that of keratin 10 and enhanced the effect of a differentiating agent on the promoter activity of involucrin, consistent with promotion of early differentiation. Glycerol inhibited DNA synthesis, whereas equivalent concentrations of xylitol or sorbitol, as osmotic controls, had no effect. Direct provision of PG, but not phosphatidylpropanol, inhibited DNA synthesis in proliferative cells. Thus, our results support the idea that AQP3 supplies PLD2 with glycerol for synthesizing PG, a lipid signal that promotes early keratinocyte differentiation.
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U2 - 10.1038/sj.jid.5700921
DO - 10.1038/sj.jid.5700921
M3 - Article
C2 - 17597824
AN - SCOPUS:36248968667
SN - 0022-202X
VL - 127
SP - 2823
EP - 2831
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 12
ER -