Aquaporin-3 re-expression induces differentiation in a phospholipase D2-dependent manner in aquaporin-3-knockout mouse keratinocytes

Vivek Choudhary, Lawrence O. Olala, Haixia Qin, Inas Helwa, Zhi Qiang Pan, Ying Ying Tsai, Michael A. Frohman, Ismail Kaddour-Djebbar, Wendy B. Bollag

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Aquaporin-3 (AQP3) is a water and glycerol channel expressed in epidermal keratinocytes. Despite many studies, controversy remains about the role of AQP3 in keratinocyte differentiation. Previously, our laboratory has shown co-localization of AQP3 and phospholipase D2 (PLD2) in caveolin-rich membrane microdomains. We hypothesized that AQP3 transports glycerol and "funnels" this primary alcohol to PLD2 to form a pro-differentiative signal, such that the action of AQP3 to induce differentiation should require PLD2. To test this idea, we re-expressed AQP3 in mouse keratinocytes derived from AQP3-knockout mice. The re-expression of AQP3, which increased [3H]glycerol uptake, also induced mRNA and protein expression of epidermal differentiation markers such as keratin 1, keratin 10, and loricrin, with or without the induction of differentiation by an elevated extracellular calcium concentration. Re-expression of AQP3 had no effect on the expression of the proliferation markers keratin 5 and cyclin D1. Furthermore, a selective inhibitor of PLD2, CAY10594, and a lipase-dead (LD) PLD2 mutant, but not a LD PLD1 mutant, significantly inhibited AQP3 re-expression-induced differentiation marker expression with calcium elevation, suggesting a role for PLD2 in this process. Thus, our results indicate that AQP3 has a pro-differentiative role in epidermal keratinocytes and that PLD2 activity is necessary for this effect.

Original languageEnglish (US)
Pages (from-to)499-507
Number of pages9
JournalJournal of Investigative Dermatology
Volume135
Issue number2
DOIs
StatePublished - Feb 13 2015

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Aquaporin 3
Keratinocytes
Knockout Mice
Glycerol
Differentiation Antigens
Lipase
phospholipase D2
Keratin-1
Keratin-10
Keratin-5
Membrane Microdomains
Caveolins
Calcium
Aquaporins
Cyclin D1

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

Aquaporin-3 re-expression induces differentiation in a phospholipase D2-dependent manner in aquaporin-3-knockout mouse keratinocytes. / Choudhary, Vivek; Olala, Lawrence O.; Qin, Haixia; Helwa, Inas; Pan, Zhi Qiang; Tsai, Ying Ying; Frohman, Michael A.; Kaddour-Djebbar, Ismail; Bollag, Wendy B.

In: Journal of Investigative Dermatology, Vol. 135, No. 2, 13.02.2015, p. 499-507.

Research output: Contribution to journalArticle

Choudhary, Vivek ; Olala, Lawrence O. ; Qin, Haixia ; Helwa, Inas ; Pan, Zhi Qiang ; Tsai, Ying Ying ; Frohman, Michael A. ; Kaddour-Djebbar, Ismail ; Bollag, Wendy B. / Aquaporin-3 re-expression induces differentiation in a phospholipase D2-dependent manner in aquaporin-3-knockout mouse keratinocytes. In: Journal of Investigative Dermatology. 2015 ; Vol. 135, No. 2. pp. 499-507.
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AU - Olala, Lawrence O.

AU - Qin, Haixia

AU - Helwa, Inas

AU - Pan, Zhi Qiang

AU - Tsai, Ying Ying

AU - Frohman, Michael A.

AU - Kaddour-Djebbar, Ismail

AU - Bollag, Wendy B.

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