Evidence for a causal link between adaptor protein PDZK1 downregulation and Na+/H+ exchanger NHE3 dysfunction in human and murine colitis

Pflugers Archiv European Journal of Physiology

Volumn 467, Issue 8, 2015, Pages 1795-1807

  Yeruva, Sunil ^a   Chodisetti, Giriprakash ^a   Luo, Min ^a   Chen, Mingmin ^a,f   Cinar, Ayhan ^a,g   Ludolph, Lisa ^a   Lünnemann, Maria ^a   Goldstein, Julia ^a   Singh, Anurag Kumar ^a   Riederer, Brigitte ^a   Bachmann, Oliver ^a   Bleich, Andre ^a   Gereke, Markus ^b,e   Bruder, Dunja ^b,e   Hagen, Susan ^c   He, Peijian ^d   Yun, Chris ^d   Seidler, Ursula ^a  

^a HANNOVER MEDICAL SCHOOL   (Germany)

^b HELMHOLTZ CENTRE FOR INFECTION RESEARCH   (Germany)

^c Division of Endocrinology   (United States)

^d EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

^e OTTO VON GUERICKE UNIVERSITY   (Germany)

^f SHAOXING UNIVERSITY   (China)

^g MINISTRY OF HEALTH   (Turkey)

Author keywords

Electrolyte transport; Inflammatory bowel disease; Intestinal inflammation; pH regulation; Sodium absorption

Indexed keywords

ADAPTOR PROTEIN; GAMMA INTERFERON; INTERLEUKIN 1BETA; MESSENGER RNA; PDZK1 PROTEIN; SHORT HAIRPIN RNA; SODIUM PROTON EXCHANGE PROTEIN 3; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; AUTACOID; CARRIER PROTEIN; DEXTRAN SULFATE; DNA BINDING PROTEIN; IL10 PROTEIN, MOUSE; INTERLEUKIN 10; PDZK1 PROTEIN, HUMAN; PDZK1 PROTEIN, MOUSE; RAG2 PROTEIN, MOUSE; SIGNAL PEPTIDE; SODIUM PROTON EXCHANGE PROTEIN; SODIUM-HYDROGEN EXCHANGER 3; TUMOR NECROSIS FACTOR;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BRUSH BORDER; COLON BIOPSY; COLON MUCOSA; CONTROLLED STUDY; DOWN REGULATION; EXPERIMENTAL COLITIS; HUMAN; HUMAN TISSUE; ILEUM MUCOSA; INTESTINE CELL; NONHUMAN; PRIORITY JOURNAL; PROTEIN CONTENT; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; 129 MOUSE; ANIMAL; BIOPSY; CACO-2 CELL LINE; CHEMICALLY INDUCED; COLITIS; COLON; DEFICIENCY; DISEASE MODEL; GENETIC TRANSFECTION; GENETICS; ILEITIS; ILEUM; KNOCKOUT MOUSE; METABOLISM; MICROVILLUS; PATHOLOGY; RETROSPECTIVE STUDY; RNA INTERFERENCE;

ANIMALS; BIOPSY; CACO-2 CELLS; CARRIER PROTEINS; COLITIS; COLON; DEXTRAN SULFATE; DISEASE MODELS, ANIMAL; DNA-BINDING PROTEINS; DOWN-REGULATION; ENTEROCYTES; HUMANS; ILEITIS; ILEUM; INFLAMMATION MEDIATORS; INTERLEUKIN-10; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; MICE, 129 STRAIN; MICE, KNOCKOUT; MICROVILLI; RETROSPECTIVE STUDIES; RNA INTERFERENCE; RNA, MESSENGER; SODIUM-HYDROGEN ANTIPORTER; TRANSFECTION; TUMOR NECROSIS FACTOR-ALPHA;

EID: 84937805444     PISSN: 00316768     EISSN: 14322013     Source Type: Journal    
DOI: 10.1007/s00424-014-1608-x     Document Type: Article

References (42)

1. Alexander RT, Grinstein S (2009) Tethering, recycling and activation of the epithelial sodium-proton exchanger, NHE3. J Exp Biol 212(Pt 11):1630–1637. doi:10.1242/jeb.027375
2. Amasheh M, Grotjohann I, Amasheh S, Fromm A, Soderholm JD, Zeitz M, Fromm M, Schulzke JD (2009) Regulation of mucosal structure and barrier function in rat colon exposed to tumor necrosis factor alpha and interferon gamma in vitro: a novel model for studying the pathomechanisms of inflammatory bowel disease cytokines. Scand J Gastroenterol 44(10):1226–1235. doi:10.1080/00365520903131973
3. Bachmann O, Riederer B, Rossmann H, Groos S, Schultheis PJ, Shull GE, Gregor M, Manns MP, Seidler U (2004) The Na+/H+ exchanger isoform 2 is the predominant NHE isoform in murine colonic crypts and its lack causes NHE3 upregulation. Am J Physiol Gastrointest Liver Physiol 287(1):G125–G133. doi:10.1152/ajpgi.00332.2003
4. Barmeyer C, Harren M, Schmitz H, Heinzel-Pleines U, Mankertz J, Seidler U, Horak I, Wiedenmann B, Fromm M, Schulzke JD (2004) Mechanisms of diarrhea in the interleukin-2-deficient mouse model of colonic inflammation. Am J Physiol Gastrointest Liver Physiol 286(2):G244–G252. doi:10.1152/ajpgi.00141.2003
5. Biber J, Gisler SM, Hernando N, Murer H (2005) Protein/protein interactions (PDZ) in proximal tubules. J Membr Biol 203(3):111–118. doi:10.1007/s00232-005-0738-7
6. Bleich A, Mahler M, Most C, Leiter EH, Liebler-Tenorio E, Elson CO, Hedrich HJ, Schlegelberger B, Sundberg JP (2004) Refined histopathologic scoring system improves power to detect colitis QTL in mice. Mamm Genome 15(11):865–871
7. Broere N, Chen M, Cinar A, Singh AK, Hillesheim J, Riederer B, Lunnemann M, Rottinghaus I, Krabbenhoft A, Engelhardt R, Rausch B, Weinman EJ, Donowitz M, Hubbard A, Kocher O, de Jonge HR, Hogema BM, Seidler U (2009) Defective jejunal and colonic salt absorption and altered Na(+)/H(+) exchanger 3 (NHE3) activity in NHE regulatory factor 1 (NHERF1) adaptor protein-deficient mice. Pflugers Arch 457(5):1079–1091. doi:10.1007/s00424-008-0579-1
8. Chen M, Sultan A, Cinar A, Yeruva S, Riederer B, Singh AK, Li J, Bonhagen J, Chen G, Yun C, Donowitz M, Hogema B, de Jonge H, Seidler U (2011) Loss of PDZ-adaptor protein NHERF2 affects membrane localization and cGMP- and [Ca2+]- but not cAMP-dependent regulation of Na+/H+ exchanger 3 in murine intestine. J Physiol 588(Pt 24):5049–5063. doi:10.1113/jphysiol.2010.198721
9. Cinar A, Chen M, Riederer B, Bachmann O, Wiemann M, Manns M, Kocher O, Seidler U (2007) NHE3 inhibition by cAMP and Ca2+ is abolished in PDZ-domain protein PDZK1-deficient murine enterocytes. J Physiol 581(Pt 3):1235–1246. doi:10.1113/jphysiol.2007.131722
10. Clayburgh DR, Musch MW, Leitges M, Fu YX, Turner JR (2006) Coordinated epithelial NHE3 inhibition and barrier dysfunction are required for TNF-mediated diarrhea in vivo. J Clin Invest 116(10):2682–2694. doi:10.1172/JCI29218
11. Donowitz M, Li X (2007) Regulatory binding partners and complexes of NHE3. Physiol Rev 87(3):825–872. doi:10.1152/physrev.00030.2006
12. Donowitz M, Mohan S, Zhu CX, Chen TE, Lin R, Cha B, Zachos NC, Murtazina R, Sarker R, Li X (2009) NHE3 regulatory complexes. J Exp Biol 212(Pt 11):1638–1646. doi:10.1242/jeb.028605
13. Farkas K, Yeruva S, Rakonczay Z Jr, Ludolph L, Molnar T, Nagy F, Szepes Z, Schnur A, Wittmann T, Hubricht J, Riederer B, Venglovecz V, Lazar G, Kiraly M, Zsembery A, Varga G, Seidler U, Hegyi P (2011) New therapeutic targets in ulcerative colitis: the importance of ion transporters in the human colon. Inflamm Bowel Dis 17(4):884–898. doi:10.1002/ibd.21432
14. Gisler SM, Madjdpour C, Bacic D, Pribanic S, Taylor SS, Biber J, Murer H (2003) PDZK1: II. an anchoring site for the PKA-binding protein D-AKAP2 in renal proximal tubular cells. Kidney Int 64(5):1746–1754. doi:10.1046/j.1523-1755.2003.00267
15. Hagen SJ, Trier JS, Dambrauskas R (1994) Exposure of the rat small intestine to raw kidney beans results in reorganization of absorptive cell microvilli. Gastroenterology 106(1):73–84
16. Harmon GS, Dumlao DS, Ng DT, Barrett KE, Dennis EA, Dong H, Glass CK (2010) Pharmacological correction of a defect in PPAR-gamma signaling ameliorates disease severity in Cftr-deficient mice. Nat Med 16(3):313–318. doi:10.1038/nm.2101
17. He P, Yun CC (2010) Mechanisms of the regulation of the intestinal Na+/H+ exchanger NHE3. J Biomed Biotechnol 2010:238080. doi:10.1155/2010/238080
18. He P, Zhang H, Yun CC (2008) IRBIT, inositol 1,4,5-triphosphate (IP3) receptor-binding protein released with IP3, binds Na+/H+ exchanger NHE3 and activates NHE3 activity in response to calcium. J Biol Chem 283(48):33544–33553. doi:10.1074/jbc.M805534200
19. Hillesheim J, Riederer B, Tuo B, Chen M, Manns M, Biber J, Yun C, Kocher O, Seidler U (2007) Down regulation of small intestinal ion transport in PDZK1- (CAP70/NHERF3) deficient mice. Pflugers Arch 454(4):575–586. doi:10.1007/s00424-007-0239-x
20. Juric M, Xiao F, Amasheh S, May O, Wahl K, Bantel H, Manns MP, Seidler U, Bachmann O (2013) Increased epithelial permeability is the primary cause for bicarbonate loss in inflamed murine colon. Inflamm Bowel Dis 19(5):904–911. doi:10.1097/MIB.0b013e3182813322
21. LaLonde DP, Garbett D, Bretscher A (2010) A regulated complex of the scaffolding proteins PDZK1 and EBP50 with ezrin contribute to microvillar organization. Mol Biol Cell 21(9):1519–1529. doi:10.1091/mbc.E10-01-0008
22. Lamprecht G, Seidler U (2006) The emerging role of PDZ adapter proteins for regulation of intestinal ion transport. Am J Physiol Gastrointest Liver Physiol 291(5):G766–G777. doi:10.1152/ajpgi.00135.2006
23. Lefkimmiatis K, Zaccolo M (2014) cAMP signaling in subcellular compartments. Pharmacol Ther 143(3):295–304. doi:10.1016/j.pharmthera.2014.03.008
24. Lenzen H, Lunnemann M, Bleich A, Manns MP, Seidler U, Jorns A (2012) Downregulation of the NHE3-binding PDZ-adaptor protein PDZK1 expression during cytokine-induced inflammation in interleukin-10-deficient mice. PLoS One 7(7):e40657. doi:10.1371/journal.pone.0040657
25. Lin S, Yeruva S, He P, Singh AK, Zhang H, Chen M, Lamprecht G, de Jonge HR, Tse M, Donowitz M, Hogema BM, Chun J, Seidler U, Yun CC (2010) Lysophosphatidic acid stimulates the intestinal brush border Na(+)/H(+) exchanger 3 and fluid absorption via LPA(5) and NHERF2. Gastroenterology 138(2):649–658. doi:10.1053/j.gastro.2009.09.055
26. Lohi H, Makela S, Pulkkinen K, Hoglund P, Karjalainen-Lindsberg ML, Puolakkainen P, Kere J (2002) Upregulation of CFTR expression but not SLC26A3 and SLC9A3 in ulcerative colitis. Am J Physiol Gastrointest Liver Physiol 283(3):G567–G575. doi:10.1152/ajpgi.00356.2001
27. Monterisi S, Casavola V, Zaccolo M (2013) Local modulation of cystic fibrosis conductance regulator: cytoskeleton and compartmentalized cAMP signalling. Br J Pharmacol 169(1):1–9. doi:10.1111/bph.12017
28. Musch MW, Clarke LL, Mamah D, Gawenis LR, Zhang Z, Ellsworth W, Shalowitz D, Mittal N, Efthimiou P, Alnadjim Z, Hurst SD, Chang EB, Barrett TA (2002) T cell activation causes diarrhea by increasing intestinal permeability and inhibiting epithelial Na+/K+-ATPase. J Clin Invest 110(11):1739–1747. doi:10.1172/JCI15695
29. Pfaffl MW (2001) A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29(9):e45
30. Preisig PA (2007) The acid-activated signaling pathway: starting with Pyk2 and ending with increased NHE3 activity. Kidney Int 72(11):1324–1329. doi:10.1038/sj.ki.5002543
31. Ritchie JM, Rui H, Zhou X, Iida T, Kodoma T, Ito S, Davis BM, Bronson RT, Waldor MK (2012) Inflammation and disintegration of intestinal villi in an experimental model for Vibrio parahaemolyticus-induced diarrhea. PLoS Pathog 8(3):e1002593. doi:10.1371/journal.ppat.1002593
32. Sarker R, Valkhoff VE, Zachos NC, Lin R, Cha B, Chen TE, Guggino S, Zizak M, de Jonge H, Hogema B, Donowitz M (2011) NHERF1 and NHERF2 are necessary for multiple but usually separate aspects of basal and acute regulation of NHE3 activity. Am J Physiol Cell Physiol 300(4):C771–C782. doi:10.1152/ajpcell.00119.2010
33. Shah SB, Hanauer SB (2007) Treatment of diarrhea in patients with inflammatory bowel disease: concepts and cautions. Rev Gastroenterol Disord 7(Suppl 3):S3–S10
34. Sullivan S, Alex P, Dassopoulos T, Zachos NC, Iacobuzio-Donahue C, Donowitz M, Brant SR, Cuffari C, Harris ML, Datta LW, Conklin L, Chen Y, Li X (2009) Downregulation of sodium transporters and NHERF proteins in IBD patients and mouse colitis models: potential contributors to IBD-associated diarrhea. Inflamm Bowel Dis 15(2):261–274. doi:10.1002/ibd.20743
35. Sultan A, Luo M, Yu Q, Riederer B, Xia W, Chen M, Lissner S, Gessner JE, Donowitz M, Yun CC, deJonge H, Lamprecht G, Seidler U (2013) Differential association of the Na+/H+ exchanger regulatory factor (NHERF) family of adaptor proteins with the raft- and the non-raft brush border membrane fractions of NHE3. Cell Physiol Biochem 32(5):1386–1402. doi:10.1159/000356577
36. Tachibana K, Anzai N, Ueda C, Katayama T, Yamasaki D, Kirino T, Takahashi R, Ishimoto K, Komori H, Tanaka T, Hamakubo T, Ueda Y, Arai H, Sakai J, Kodama T, Doi T (2008) Regulation of the human PDZK1 expression by peroxisome proliferator-activated receptor alpha. FEBS Lett 582(28):3884–3888. doi:10.1016/j.febslet.2008.10.027
37. Tse CM, Levine SA, Yun CH, Brant SR, Pouyssegur J, Montrose MH, Donowitz M (1993) Functional characteristics of a cloned epithelial Na+/H+ exchanger (NHE3): resistance to amiloride and inhibition by protein kinase C. Proc Natl Acad Sci U S A 90(19):9110–9114
38. Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A, Speleman F (2002) Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol 3(7):RESEARCH0034
39. Xiao F, Juric M, Li J, Riederer B, Yeruva S, Singh AK, Zheng L, Glage S, Kollias G, Dudeja P, Tian DA, Xu G, Zhu J, Bachmann O, Seidler U (2011) Loss of downregulated in adenoma (DRA) impairs mucosal HCO3(-) secretion in murine ileocolonic inflammation. Inflamm Bowel Dis 18(1):101–111. doi:10.1002/ibd.21744
40. Yeruva S, Farkas K, Hubricht J, Rode K, Riederer B, Bachmann O, Cinar A, Rakonczay Z, Molnar T, Nagy F, Wedemeyer J, Manns M, Raddatz D, Musch MW, Chang EB, Hegyi P, Seidler U (2010) Preserved Na(+)/H(+) exchanger isoform 3 expression and localization, but decreased NHE3 function indicate regulatory sodium transport defect in ulcerative colitis. Inflamm Bowel Dis 16(7):1149–1161. doi:10.1002/ibd.21183
41. Zachos NC, Li X, Kovbasnjuk O, Hogema B, Sarker R, Lee LJ, Li M, de Jonge H, Donowitz M (2009) NHERF3 (PDZK1) contributes to basal and calcium inhibition of NHE3 activity in Caco-2BBe cells. J Biol Chem 284(35):23708–23718. doi:10.1074/jbc.M109.012641
42. Zeissig S, Bergann T, Fromm A, Bojarski C, Heller F, Guenther U, Zeitz M, Fromm M, Schulzke JD (2008) Altered ENaC expression leads to impaired sodium absorption in the noninflamed intestine in Crohn’s disease. Gastroenterology 134(5):1436–1447. doi:10.1053/j.gastro.2008.02.030