Lysophosphatidic acid induces exocytic trafficking of Na+/H + exchanger 3 by E3KARP-dependent activation of phospholipase C

Jung Woong Choi, Whaseon Lee-Kwon, Eun Su Jeon, Yong Jung Kang, Kazuya Kawano, Hyeon Soo Kim, Pann Ghill Suh, Mark Donowitz, Jae Ho Kim

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Lysophosphatidic acid (LPA) stimulates Na+/H+ exchanger 3 (NHE3) activity in opossum kidney proximal tubule (OK) cells by increasing the apical membrane amount of NHE3. This occurs by stimulation of exocytic trafficking of NHE3 to the apical plasma membrane by an E3KARP-dependent mechanism. However, it is still unclear how E3KARP leads to the LPA-induced exocytosis of NHE3. In the current study, we demonstrate that stable expression of exogenous E3KARP increases LPA-induced phospholipase C (PLC) activation and subsequent elevation of intracellular Ca2+ in opossum kidney proximal tubule (OK) cells. Pretreatment with U73122, a PLC inhibitor, prevented the LPA-induced NHE3 activation and the exocytic trafficking of NHE3. To understand how the elevation of intracellular Ca 2+ leads to the stimulation of NHE3, we pretreated OK cells with BAPTA-AM, an intracellular Ca2+ chelator. BAPTA-AM completely blocked the LPA-induced increase of NHE3 activity and surface NHE3 amount by decreasing the LPA-induced exocytic trafficking of NHE3. Pretreatment with GF109203X, a PKC inhibitor, did not affect the percent of LPA-induced NHE3 activation and increase of surface NHE3 amount. From these results, we suggest that E3KARP plays a necessary role in LPA-induced PLC activation, and that PLC-dependent elevation of intracellular Ca2+ but not PKC activation is necessary for the LPA-induced increase of NHE3 exocytosis.

Original languageEnglish
Pages (from-to)59-68
Number of pages10
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1683
Issue number1-3
DOIs
Publication statusPublished - 2004 Jul 5

Keywords

  • Calcium
  • E3KARP
  • Exocytosis
  • G protein-coupled receptor
  • GPCR
  • LPA
  • NHE3
  • Na/H exchanger 3
  • OK cells
  • PDZ
  • PLC
  • PSD-95/Dlg-1/ZO-1
  • Phospholipase C
  • lysophosphatidic acid
  • opossum kidney proximal tubule cells
  • phospholipase C

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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