1932

Abstract

Systems biology can be defined as the study of a biological process in which all of the relevant components are investigated together in parallel to discover the mechanism. Although the approach is not new, it has come to the forefront as a result of genome sequencing projects completed in the first few years of the current century. It has elements of large-scale data acquisition (chiefly next-generation sequencing–based methods and protein mass spectrometry) and large-scale data analysis (big data integration and Bayesian modeling). Here we discuss these methodologies and show how they can be applied to understand the downstream effects of GPCR signaling, specifically looking at how the neurohypophyseal peptide hormone vasopressin, working through the V2 receptor and PKA activation, regulates the water channel aquaporin-2. The emerging picture provides a detailedframework for understanding the molecular mechanisms involved in water balance disorders, pointing the way to improved treatment of both polyuric disorders and water-retention disorders causing dilutional hyponatremia.

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2022-01-06
2024-06-15
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Literature Cited

  1. 1. 
    Knepper MA, Kwon TH, Nielsen S. 2015. Molecular physiology of water balance. N. Engl. J. Med. 372:1349–58
    [Google Scholar]
  2. 2. 
    Upadhyay A, Jaber BL, Madias NE. 2006. Incidence and prevalence of hyponatremia. Am. J. Med. 119:S30–35
    [Google Scholar]
  3. 3. 
    Bockenhauer D, Bichet DG. 2015. Pathophysiology, diagnosis and management of nephrogenic diabetes insipidus. Nat. Rev. Nephrol. 11:576–88
    [Google Scholar]
  4. 4. 
    Refardt J, Winzeler B, Christ-Crain M. 2020. Diabetes insipidus: an update. Endocrinol. Metab. Clin. N. Am. 49:517–31
    [Google Scholar]
  5. 5. 
    Verbalis JG. 2020. Commentary: evidence-based medicine for SIAD. J. Clin. Endocrinol. Metab. 106:e1042–43
    [Google Scholar]
  6. 6. 
    Verbalis JG, Goldsmith SR, Greenberg A, Korzelius C, Schrier RW et al. 2013. Diagnosis, evaluation, and treatment of hyponatremia: expert panel recommendations. Am. J. Med. 126:S1–42
    [Google Scholar]
  7. 7. 
    Verney EB. 1947. The antidiuretic hormone and the factors which determine its release. Proc. R. Soc. Lond. B Biol. Sci. 135:25–106
    [Google Scholar]
  8. 8. 
    Baumann G, Dingman JF. 1976. Distribution, blood transport, and degradation of antidiuretic hormone in man. J. Clin. Investig. 57:1109–16
    [Google Scholar]
  9. 9. 
    Fenton RA, Knepper MA. 2007. Mouse models and the urinary concentrating mechanism in the new millennium. Physiol. Rev. 87:1083–112
    [Google Scholar]
  10. 10. 
    Bichet DG. 2019. Regulation of thirst and vasopressin release. Annu. Rev. Physiol. 81:359–73
    [Google Scholar]
  11. 11. 
    Zimmerman CA, Huey EL, Ahn JS, Beutler LR, Tan CL et al. 2019. A gut-to-brain signal of fluid osmolarity controls thirst satiation. Nature 568:98–102
    [Google Scholar]
  12. 12. 
    Star RA, Nonoguchi H, Balaban R, Knepper MA. 1988. Calcium and cyclic adenosine monophosphate as second messengers for vasopressin in the rat inner medullary collecting duct. J. Clin. Investig. 81:1879–88
    [Google Scholar]
  13. 13. 
    Yip KP. 2002. Coupling of vasopressin-induced intracellular Ca2+ mobilization and apical exocytosis in perfused rat kidney collecting duct. J. Physiol. 538:891–99
    [Google Scholar]
  14. 14. 
    Pisitkun T, Jacob V, Schleicher SM, Chou CL, Yu MJ, Knepper MA 2008. Akt and ERK1/2 pathways are components of the vasopressin signaling network in rat native IMCD. Am. J. Physiol. Renal. Physiol. 295:F1030–43
    [Google Scholar]
  15. 15. 
    Chou CL, Rapko SI, Knepper MA. 1998. Phosphoinositide signaling in rat inner medullary collecting duct. Am. J. Physiol. 274:F564–72
    [Google Scholar]
  16. 16. 
    Isobe K, Jung HJ, Yang CR, Claxton J, Sandoval P et al. 2017. Systems-level identification of PKA-dependent signaling in epithelial cells. PNAS 114:E8875–84
    [Google Scholar]
  17. 17. 
    Datta A, Yang CR, Limbutara K, Chou CL, Rinschen MM et al. 2020. PKA-independent vasopressin signaling in renal collecting duct. FASEB J 34:6129–46
    [Google Scholar]
  18. 18. 
    Salhadar K, Matthews A, Raghuram V, Limbutara K, Yang CR et al. 2021. Phosphoproteomic identification of vasopressin/cAMP/PKA-dependent signaling in kidney. Mol. Pharmacol. 99:358–69
    [Google Scholar]
  19. 19. 
    Ranieri M, Di Mise A, Tamma G, Valenti G 2019. Vasopressin-aquaporin-2 pathway: recent advances in understanding water balance disorders. F1000Res 8:149
    [Google Scholar]
  20. 20. 
    Jung HJ, Kwon TH. 2016. Molecular mechanisms regulating aquaporin-2 in kidney collecting duct. Am. J. Physiol. Ren. Physiol. 311:F1318–28
    [Google Scholar]
  21. 21. 
    Tohgo A, Choy EW, Gesty-Palmer D, Pierce KL, Laporte S et al. 2003. The stability of the G protein-coupled receptor-β-arrestin interaction determines the mechanism and functional consequence of ERK activation. J. Biol. Chem. 278:6258–67
    [Google Scholar]
  22. 22. 
    Rinschen MM, Yu MJ, Wang G, Boja ES, Hoffert JD et al. 2010. Quantitative phosphoproteomic analysis reveals vasopressin V2-receptor-dependent signaling pathways in renal collecting duct cells. PNAS 107:3882–87
    [Google Scholar]
  23. 23. 
    Datta A, Yang CR, Salhadar K, Park E, Chou CL et al. 2021. Phosphoproteomic identification of vasopressin-regulated protein kinases in collecting duct cells. Br. J. Pharmacol. 178:1426–44
    [Google Scholar]
  24. 24. 
    Nielsen S, Frøkiaer J, Marples D, Kwon TH, Agre P, Knepper MA 2002. Aquaporins in the kidney: from molecules to medicine. Physiol. Rev. 82:205–44
    [Google Scholar]
  25. 25. 
    Nielsen S, Chou CL, Marples D, Christensen EI, Kishore BK, Knepper MA. 1995. Vasopressin increases water permeability of kidney collecting duct by inducing translocation of aquaporin-CD water channels to plasma membrane. PNAS 92:1013–17
    [Google Scholar]
  26. 26. 
    Nielsen S, Knepper MA. 1993. Vasopressin activates collecting duct urea transporters and water channels by distinct physical processes. Am. J. Physiol. 265:F204–13
    [Google Scholar]
  27. 27. 
    Brown D. 2003. The ins and outs of aquaporin-2 trafficking. Am. J. Physiol. Ren. Physiol. 284:F893–901
    [Google Scholar]
  28. 28. 
    Nishimoto G, Zelenina M, Li D, Yasui M, Aperia A et al. 1999. Arginine vasopressin stimulates phosphorylation of aquaporin-2 in rat renal tissue. Am. J. Physiol. 276:F254–59
    [Google Scholar]
  29. 29. 
    Hoffert JD, Pisitkun T, Wang G, Shen RF, Knepper MA. 2006. Quantitative phosphoproteomics of vasopressin-sensitive renal cells: regulation of aquaporin-2 phosphorylation at two sites. PNAS 103:7159–64
    [Google Scholar]
  30. 30. 
    Hoffert JD, Fenton RA, Moeller HB, Simons B, Tchapyjnikov D et al. 2008. Vasopressin-stimulated increase in phosphorylation at Ser269 potentiates plasma membrane retention of aquaporin-2. J. Biol. Chem. 283:24617–27
    [Google Scholar]
  31. 31. 
    Moeller HB, Praetorius J, Rützler MR, Fenton RA. 2010. Phosphorylation of aquaporin-2 regulates its endocytosis and protein-protein interactions. PNAS 107:424–29
    [Google Scholar]
  32. 32. 
    Katsura T, Gustafson CE, Ausiello DA, Brown D 1997. Protein kinase A phosphorylation is involved in regulated exocytosis of aquaporin-2 in transfected LLC-PK1 cells. Am. J. Physiol. 272:F817–22
    [Google Scholar]
  33. 33. 
    Fushimi K, Sasaki S, Marumo F. 1997. Phosphorylation of serine 256 is required for cAMP-dependent regulatory exocytosis of the aquaporin-2 water channel. J. Biol. Chem. 272:14800–4
    [Google Scholar]
  34. 34. 
    van Balkom BW, Savelkoul PJ, Markovich D, Hofman E, Nielsen S et al. 2002. The role of putative phosphorylation sites in the targeting and shuttling of the aquaporin-2 water channel. J. Biol. Chem. 277:41473–79
    [Google Scholar]
  35. 35. 
    Nedvetsky PI, Tabor V, Tamma G, Beulshausen S, Skroblin P et al. 2010. Reciprocal regulation of aquaporin-2 abundance and degradation by protein kinase A and p38-MAP kinase. J. Am. Soc. Nephrol. 21:1645–56
    [Google Scholar]
  36. 36. 
    Lu HJ, Matsuzaki T, Bouley R, Hasler U, Qin QH, Brown D. 2008. The phosphorylation state of serine 256 is dominant over that of serine 261 in the regulation of AQP2 trafficking in renal epithelial cells. Am. J. Physiol. Ren. Physiol. 295:F290–94
    [Google Scholar]
  37. 37. 
    DiGiovanni SR, Nielsen S, Christensen EI, Knepper MA. 1994. Regulation of collecting duct water channel expression by vasopressin in Brattleboro rat. PNAS 91:8984–88
    [Google Scholar]
  38. 38. 
    Kishore BK, Terris JM, Knepper MA. 1996. Quantitation of aquaporin-2 abundance in microdissected collecting ducts: axial distribution and control by AVP. Am. J. Physiol. 271:F62–70
    [Google Scholar]
  39. 39. 
    Sandoval PC, Slentz DH, Pisitkun T, Saeed F, Hoffert JD, Knepper MA. 2013. Proteome-wide measurement of protein half-lives and translation rates in vasopressin-sensitive collecting duct cells. J. Am. Soc. Nephrol. 24:1793–805
    [Google Scholar]
  40. 40. 
    Torres VE, Chapman AB, Devuyst O, Gansevoort RT, Grantham JJ et al. 2012. Tolvaptan in patients with autosomal dominant polycystic kidney disease. N. Engl. J. Med. 367:2407–18
    [Google Scholar]
  41. 41. 
    Masoumi A, Reed-Gitomer B, Kelleher C, Schrier RW. 2007. Potential pharmacological interventions in polycystic kidney disease. Drugs 67:2495–510
    [Google Scholar]
  42. 42. 
    Sussman CR, Wang X, Chebib FT, Torres VE. 2020. Modulation of polycystic kidney disease by G-protein coupled receptors and cyclic AMP signaling. Cell Signal 72:109649
    [Google Scholar]
  43. 43. 
    Miranda CA, Lee JW, Chou CL, Knepper MA. 2014. Tolvaptan as a tool in renal physiology. Am. J. Physiol. Ren. Physiol. 306:F359–66
    [Google Scholar]
  44. 44. 
    Kortenoeven ML, Sinke AP, Hadrup N, Trimpert C, Wetzels JF et al. 2013. Demeclocycline attenuates hyponatremia by reducing aquaporin-2 expression in the renal inner medulla. Am. J. Physiol. Ren. Physiol. 305:F1705–18
    [Google Scholar]
  45. 45. 
    Lockett J, Berkman KE, Dimeski G, Russell AW, Inder WJ 2019. Urea treatment in fluid restriction-refractory hyponatraemia. Clin. Endocrinol. 90:630–36
    [Google Scholar]
  46. 46. 
    Knepper MA, Miranda CA. 2013. Urea channel inhibitors: a new functional class of aquaretics. Kidney Int 83:991–93
    [Google Scholar]
  47. 47. 
    Zhang S, Zhao Y, Wang S, Li M, Xu Y et al. 2021. Discovery of novel diarylamides as orally active diuretics targeting urea transporters. Acta Pharm. Sin. B 11:181–202
    [Google Scholar]
  48. 48. 
    Li M, Zhang S, Yang B. 2020. Urea transporters identified as novel diuretic drug targets. Curr. Drug Targets 21:279–87
    [Google Scholar]
  49. 49. 
    Esteva-Font C, Anderson MO, Verkman AS 2015. Urea transporter proteins as targets for small-molecule diuretics. Nat. Rev. Nephrol. 11:113–23
    [Google Scholar]
  50. 50. 
    Sawyer WH, Acosta M, Balaspiri L, Judd J, Manning M 1974. Structural changes in the arginine vasopressin molecule that enhance antidiuretic activity and specificity. Endocrinology 94:1106–15
    [Google Scholar]
  51. 51. 
    Verbalis JG. 2003. Diabetes insipidus. Rev. Endocr. Metab. Disord. 4:177–85
    [Google Scholar]
  52. 52. 
    Sands JM, Klein JD. 2016. Physiological insights into novel therapies for nephrogenic diabetes insipidus. Am. J. Physiol. Ren. Physiol. 311:F1149–52
    [Google Scholar]
  53. 53. 
    Bockenhauer D, Bichet DG. 2017. Nephrogenic diabetes insipidus. Curr. Opin. Pediatr. 29:199–205
    [Google Scholar]
  54. 54. 
    Li JH, Chou CL, Li B, Gavrilova O, Eisner C et al. 2009. A selective EP4 PGE2 receptor agonist alleviates disease in a new mouse model of X-linked nephrogenic diabetes insipidus. J. Clin. Investig. 119:3115–26
    [Google Scholar]
  55. 55. 
    Hagner S, Stahl U, Knoblauch B, McGregor GP, Lang RE. 2002. Calcitonin receptor-like receptor: identification and distribution in human peripheral tissues. Cell Tissue Res 310:41–50
    [Google Scholar]
  56. 56. 
    Olesen ET, Moeller HB, Assentoft M, MacAulay N, Fenton RA. 2016. The vasopressin type 2 receptor and prostaglandin receptors EP2 and EP4 can increase aquaporin-2 plasma membrane targeting through a cAMP-independent pathway. Am. J. Physiol. Ren. Physiol. 311:F935–44
    [Google Scholar]
  57. 57. 
    Robert-Nicoud M, Flahaut M, Elalouf JM, Nicod M, Salinas M et al. 2001. Transcriptome of a mouse kidney cortical collecting duct cell line: effects of aldosterone and vasopressin. PNAS 98:2712–16
    [Google Scholar]
  58. 58. 
    Owada A, Nonoguchi H, Terada Y, Marumo F, Tomita K 1997. Microlocalization and effects of adrenomedullin in nephron segments and in mesangial cells of the rat. Am. J. Physiol. 272:F691–97
    [Google Scholar]
  59. 59. 
    Hay DL, Garelja ML, Poyner DR, Walker CS. 2018. Update on the pharmacology of calcitonin/CGRP family of peptides: IUPHAR review 25. Br. J. Pharmacol. 175:3–17
    [Google Scholar]
  60. 60. 
    Bogum J, Faust D, Zühlke K, Eichhorst J, Moutty MC et al. 2013. Small-molecule screening identifies modulators of aquaporin-2 trafficking. J. Am. Soc. Nephrol. 24:744–58
    [Google Scholar]
  61. 61. 
    Vukićević T, Hinze C, Baltzer S, Himmerkus N, Quintanova C et al. 2019. Fluconazole increases osmotic water transport in renal collecting duct through effects on aquaporin-2 trafficking. J. Am. Soc. Nephrol. 30:795–810
    [Google Scholar]
  62. 62. 
    Knepper MA. 2015. Systems biology of diuretic resistance. J. Clin. Investig. 125:1793–95
    [Google Scholar]
  63. 63. 
    Mast FD, Ratushny AV, Aitchison JD. 2014. Systems cell biology. J. Cell Biol. 206:695–706
    [Google Scholar]
  64. 64. 
    Rinschen MM, Limbutara K, Knepper MA, Payne DM, Pisitkun T. 2018. From molecules to mechanisms: functional proteomics and its application to renal tubule physiology. Physiol. Rev. 98:2571–606
    [Google Scholar]
  65. 65. 
    Wang Z, Gerstein M, Snyder M. 2009. RNA-Seq: a revolutionary tool for transcriptomics. Nat. Rev. Genet. 10:57–63
    [Google Scholar]
  66. 66. 
    Stark R, Grzelak M, Hadfield J. 2019. RNA sequencing: the teenage years. Nat. Rev. Genet. 20:631–56
    [Google Scholar]
  67. 67. 
    Lee JW, Chou CL, Knepper MA. 2015. Deep sequencing in microdissected renal tubules identifies nephron segment-specific transcriptomes. J. Am. Soc. Nephrol. 26:2669–77
    [Google Scholar]
  68. 68. 
    Sandoval PC, Claxton JS, Lee JW, Saeed F, Hoffert JD, Knepper MA. 2016. Systems-level analysis reveals selective regulation of Aqp2 gene expression by vasopressin. Sci. Rep. 6:34863
    [Google Scholar]
  69. 69. 
    Lee JW, Alsady M, Chou CL, de Groot T, Deen PMT et al. 2018. Single-tubule RNA-Seq uncovers signaling mechanisms that defend against hyponatremia in SIADH. Kidney Int 93:128–46
    [Google Scholar]
  70. 70. 
    Chen L, Lee JW, Chou CL, Nair AV, Battistone MA et al. 2017. Transcriptomes of major renal collecting duct cell types in mouse identified by single-cell RNA-seq. PNAS 114:E9989–98
    [Google Scholar]
  71. 71. 
    Clark JZ, Chen L, Chou CL, Jung HJ, Lee JW, Knepper MA 2019. Representation and relative abundance of cell-type selective markers in whole-kidney RNA-Seq data. Kidney Int 95:787–96
    [Google Scholar]
  72. 72. 
    Sung CC, Chen L, Limbutara K, Jung HJ, Gilmer GG et al. 2019. RNA-Seq and protein mass spectrometry in microdissected kidney tubules reveal signaling processes initiating lithium-induced nephrogenic diabetes insipidus. Kidney Int 96:363–77
    [Google Scholar]
  73. 73. 
    Matsumura Y, Uchida S, Rai T, Sasaki S, Marumo F. 1997. Transcriptional regulation of aquaporin-2 water channel gene by cAMP. J. Am. Soc. Nephrol. 8:861–67
    [Google Scholar]
  74. 74. 
    Ecelbarger CA, Nielsen S, Olson BR, Murase T, Baker EA et al. 1997. Role of renal aquaporins in escape from vasopressin-induced antidiuresis in rat. J. Clin. Investig. 99:1852–63
    [Google Scholar]
  75. 75. 
    Hasler U, Mordasini D, Bens M, Bianchi M, Cluzeaud F et al. 2002. Long term regulation of aquaporin-2 expression in vasopressin-responsive renal collecting duct principal cells. J. Biol. Chem. 277:10379–86
    [Google Scholar]
  76. 76. 
    Taylor SS, Ilouz R, Zhang P, Kornev AP. 2012. Assembly of allosteric macromolecular switches: lessons from PKA. Nat. Rev. Mol. Cell Biol. 13:646–58
    [Google Scholar]
  77. 77. 
    Sassone-Corsi P. 2012. The cyclic AMP pathway. Cold Spring Harb. Perspect. Biol. 4:a011148
    [Google Scholar]
  78. 78. 
    Ledford H, Callaway E. 2020. Pioneers of revolutionary CRISPR gene editing win chemistry Nobel. Nature 586:346–47
    [Google Scholar]
  79. 79. 
    Regev A, Teichmann SA, Lander ES, Amit I, Benoist C et al. 2017. Science forum: the Human Cell Atlas. eLife 6:e27041
    [Google Scholar]
  80. 80. 
    Chen L, Clark JZ, Nelson JW, Kaissling B, Ellison DH, Knepper MA. 2019. Renal-tubule epithelial cell nomenclature for single-cell RNA-sequencing studies. J. Am. Soc. Nephrol. 30:1358–64
    [Google Scholar]
  81. 81. 
    Chen L, Chou CL, Knepper MA. 2021. A comprehensive map of mRNAs and their isoforms across all 14 renal tubule segments of mouse. J. Am. Soc. Nephrol. 32:898–913
    [Google Scholar]
  82. 82. 
    Chen L, Chou CL, Knepper MA. 2021. Targeted single-cell RNA-seq identifies minority cell types of kidney distal nephron. J. Am. Soc. Nephrol. 32:887–97
    [Google Scholar]
  83. 83. 
    Wu H, Kirita Y, Donnelly EL, Humphreys BD. 2019. Advantages of single-nucleus over single-cell RNA sequencing of adult kidney: rare cell types and novel cell states revealed in fibrosis. J. Am. Soc. Nephrol. 30:23–32
    [Google Scholar]
  84. 84. 
    Park J, Shrestha R, Qiu C, Kondo A, Huang S et al. 2018. Single-cell transcriptomics of the mouse kidney reveals potential cellular targets of kidney disease. Science 360:758–63
    [Google Scholar]
  85. 85. 
    Ransick A, Lindström NO, Liu J, Zhu Q, Guo JJ et al. 2019. Single-cell profiling reveals sex, lineage, and regional diversity in the mouse kidney. Dev. Cell 51:399–413.e7
    [Google Scholar]
  86. 86. 
    Hnisz D, Day DS, Young RA. 2016. Insulated neighborhoods: structural and functional units of mammalian gene control. Cell 167:1188–200
    [Google Scholar]
  87. 87. 
    Zhao Z, Shilatifard A. 2019. Epigenetic modifications of histones in cancer. Genome Biol 20:245
    [Google Scholar]
  88. 88. 
    Buenrostro JD, Giresi PG, Zaba LC, Chang HY, Greenleaf WJ 2013. Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nat. Methods 10:1213–18
    [Google Scholar]
  89. 89. 
    Jung HJ, Raghuram V, Lee JW, Knepper MA 2018. Genome-wide mapping of DNA accessibility and binding sites for CREB and C/EBPβ in vasopressin-sensitive collecting duct cells. J. Am. Soc. Nephrol. 29:1490–500
    [Google Scholar]
  90. 90. 
    Wen B, Jung HJ, Chen L, Saeed F, Knepper MA 2020. NGS-integrator: an efficient tool for combining multiple NGS data tracks using minimum Bayes' factors. BMC Genom. 21:806
    [Google Scholar]
  91. 91. 
    Sheng X, Guan Y, Ma Z, Wu J, Liu Het al 2021. Mapping the genetic architecture of human traits to cell types in the kidney identifies mechanisms of disease and potential treatments. Nat. Genet 53:1322–33
    [Google Scholar]
  92. 92. 
    Plachetka A, Chayka O, Wilczek C, Melnik S, Bonifer C, Klempnauer KH. 2008. C/EBPβ induces chromatin opening at a cell-type-specific enhancer. Mol. Cell. Biol. 28:2102–12
    [Google Scholar]
  93. 93. 
    Zaret KS, Carroll JS. 2011. Pioneer transcription factors: establishing competence for gene expression. Genes Dev 25:2227–41
    [Google Scholar]
  94. 94. 
    Kortenoeven ML, Fenton RA. 2014. Renal aquaporins and water balance disorders. Biochim. Biophys. Acta 1840:1533–49
    [Google Scholar]
  95. 95. 
    Pearce D, Soundararajan R, Trimpert C, Kashlan OB, Deen PM, Kohan DE. 2015. Collecting duct principal cell transport processes and their regulation. Clin. J. Am. Soc. Nephrol. 10:135–46
    [Google Scholar]
  96. 96. 
    Zhao Y, Yang CR, Raghuram V, Parulekar J, Knepper MA. 2016. BIG: a large-scale data integration tool for renal physiology. Am. J. Physiol. Ren. Physiol. 311:F787–92
    [Google Scholar]
  97. 97. 
    Sanghi A, Zaringhalam M, Corcoran CC, Saeed F, Hoffert JD et al. 2014. A knowledge base of vasopressin actions in the kidney. Am. J. Physiol. Ren. Physiol. 307:F747–55
    [Google Scholar]
  98. 98. 
    Hwang JR, Chou CL, Medvar B, Knepper MA, Jung HJ. 2017. Identification of β-catenin-interacting proteins in nuclear fractions of native rat collecting duct cells. Am. J. Physiol. Ren. Physiol. 313:F30–46
    [Google Scholar]
  99. 99. 
    Xue Z, Chen JX, Zhao Y, Medvar B, Knepper MA 2017. Data integration in physiology using Bayes' rule and minimum Bayes' factors: deubiquitylating enzymes in the renal collecting duct. Physiol. Genom. 49:151–59
    [Google Scholar]
  100. 100. 
    LeMaire SM, Raghuram V, Grady CR, Pickering CM, Chou CL et al. 2017. Serine/threonine phosphatases and aquaporin-2 regulation in renal collecting duct. Am. J. Physiol. Ren. Physiol. 312:F84–95
    [Google Scholar]
  101. 101. 
    Yang CR, Raghuram V, Emamian M, Sandoval PC, Knepper MA. 2015. Deep proteomic profiling of vasopressin-sensitive collecting duct cells. II. Bioinformatic analysis of vasopressin signaling. Am. J. Physiol. Cell Physiol. 309:C799–812
    [Google Scholar]
  102. 102. 
    Bradford D, Raghuram V, Wilson JL, Chou CL, Hoffert JD et al. 2014. Use of LC-MS/MS and Bayes' theorem to identify protein kinases that phosphorylate aquaporin-2 at Ser256. Am. J. Physiol. Cell Physiol. 307:C123–39
    [Google Scholar]
  103. 103. 
    Trepiccione F, Pisitkun T, Hoffert JD, Poulsen SB, Capasso G et al. 2014. Early targets of lithium in rat kidney inner medullary collecting duct include p38 and ERK1/2. Kidney Int 86:757–67
    [Google Scholar]
  104. 104. 
    Chaurand P, Stoeckli M, Caprioli RM. 1999. Direct profiling of proteins in biological tissue sections by MALDI mass spectrometry. Anal. Chem. 71:5263–70
    [Google Scholar]
  105. 105. 
    Han G, Spitzer MH, Bendall SC, Fantl WJ, Nolan GP. 2018. Metal-isotope-tagged monoclonal antibodies for high-dimensional mass cytometry. Nat. Protoc. 13:2121–48
    [Google Scholar]
  106. 106. 
    Stickels RR, Murray E, Kumar P, Li J, Marshall JL et al. 2021. Highly sensitive spatial transcriptomics at near-cellular resolution with Slide-seqV2. Nat. Biotechnol. 39:313–19
    [Google Scholar]
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