Lysophosphatidic acid induces exocytic trafficking of Na+/H+ exchanger 3 by E3KARP-dependent activation of phospholipase C
| Autor: | Jae Ho Kim, Kazuya Kawano, Yong Jung Kang, Pann-Ghill Suh, Eun Su Jeon, Mark Donowitz, Whaseon Lee-Kwon, Jung Woong Choi, Hyeon Soo Kim |
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| Rok vydání: | 2004 |
| Předmět: |
Indoles
Sodium-Hydrogen Exchangers Stimulation CHO Cells Biology Exocytosis Kidney Tubules Proximal Maleimides chemistry.chemical_compound Cricetinae Lysophosphatidic acid Animals Enzyme Inhibitors Egtazic Acid Molecular Biology Cells Cultured Protein Kinase C Protein kinase C Chelating Agents Phospholipase C Sodium-Hydrogen Exchanger 3 urogenital system Cell Membrane Opossums Cell Biology Apical membrane Cell biology Cytoskeletal Proteins Protein Transport Sodium–hydrogen antiporter chemistry Type C Phospholipases Calcium lipids (amino acids peptides and proteins) Lysophospholipids biological phenomena cell phenomena and immunity Intracellular Signal Transduction |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. 1683:59-68 |
| ISSN: | 1388-1981 |
| DOI: | 10.1016/j.bbalip.2004.04.005 |
| Popis: | 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 Ca(2+) 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 Ca(2+) 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 Ca(2+) but not PKC activation is necessary for the LPA-induced increase of NHE3 exocytosis. |
| Databáze: | OpenAIRE |
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