Regulation of SGLT expression and localization through Epac/PKA-dependent caveolin-1 and F-actin activation in renal proximal tubule cells

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• 作者：Yu Jin Lee^a ; Mi Ok Kim^a ; Jung Min Ryu^a ; Ho Jae Han^b ; ^{hjhan@snu.ac.kr}
• 关键词：Lipid rafts ; Caveolin-1 ; Adenosine 3&prime ; 5&prime ; -cyclic monophosphate (cAMP) ; Na+-glucose cotransporters (SGLTs) ; Exchange protein directly activated by cAMP (Epac) ; Filamentous actin (F-actin)
• 刊名：Biochimica et Biophysica Acta (BBA)/Molecular Cell Research
• 出版年：2012
• 期刊代码：20_01674889
• 类别：bio
• 出版时间：April, 2012
• 卷：1823
• 期：4
• 页码：971-982
• 文件大小：2541 K

摘要

This study demonstrated that exchange proteins directly activated by cAMP (Epac) and protein kinase A (PKA) by 8-bromo (8-Br)-adenosine 3鈥?5鈥?cyclic monophosphate (cAMP) stimulated [¹⁴C]-伪-methyl-D-glucopyranoside (伪-MG) uptake through increased sodium-glucose cotransporters (SGLTs) expression and translocation to lipid rafts in renal proximal tubule cells (PTCs). In PTCs, SGLTs were colocalized with lipid raft caveolin-1 (cav-1), disrupted by methyl-尾-cyclodextrin (M尾CD). Selective activators of Epac or PKA, 8-Br-cAMP, and forskolin stimulated expressions of SGLTs and 伪-MG uptake in PTCs. In addition, 8-Br-cAMP-induced PKA and Epac activation increased phosphorylation of extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (MAPK), and nuclear factor kappa B (NF-魏B), which were involved in expressions of SGLTs. Furthermore, 8-Br-cAMP stimulated SGLTs translocation to lipid rafts via filamentous actin (F-actin) organization, which was blocked by cytochalasin D. In addition, cav-1 and SGLTs stimulated by 8-Br-cAMP were detected in lipid rafts, which were blocked by cytochalasin D. Furthermore, 8-Br-cAMP-induced SGLTs translocation and 伪-MG uptake were attenuated by inhibition of cav-1 activation with cav-1 small interfering RNA (siRNA) and inhibition of F-actin organization with TRIO and F-actin binding protein (TRIOBP). In conclusion, 8-Br-cAMP stimulated 伪-MG uptake via Epac and PKA-dependent SGLTs expression and trafficking through cav-1 and F-actin in PTCs.