Advances in slit diaphragm signaling

Current Opinion in Nephrology and Hypertension

Volumn 23, Issue 4, 2014, Pages 420-430

  New, Laura A ^a   Martin, Claire E ^a   Jones, Nina ^a  

^a UNIVERSITY OF GUELPH   (Canada)

Author keywords

Actin cytoskeleton; Nephrin; Phosphorylation; Podocyte; Slit diaphragm

Indexed keywords

ACTIN; NEPHRIN; PROTEIN CDC42; RAC1 PROTEIN; RHO GUANINE NUCLEOTIDE BINDING PROTEIN; RHOA GUANINE NUCLEOTIDE BINDING PROTEIN; MEMBRANE PROTEIN;

ACTIN FILAMENT; CHRONIC KIDNEY DISEASE; ENDOCYTOSIS; FOCAL GLOMERULOSCLEROSIS; GLOMERULAR FILTRATION BARRIER; GLOMERULOPATHY; HUMAN; NEPHROTIC SYNDROME; NONHUMAN; PATHOPHYSIOLOGY; PODOCYTE; PODOCYTE SLIT DIAPHRAGM; PRIORITY JOURNAL; PROTEIN FAMILY; PROTEIN PHOSPHORYLATION; REGULATORY MECHANISM; REVIEW; SIGNAL TRANSDUCTION; ANIMAL; CELL JUNCTION; GLOMERULUS; METABOLISM; PHYSIOLOGY;

ACTINS; ANIMALS; CDC42 GTP-BINDING PROTEIN; ENDOCYTOSIS; HUMANS; INTERCELLULAR JUNCTIONS; KIDNEY GLOMERULUS; MEMBRANE PROTEINS; PODOCYTES; RAC1 GTP-BINDING PROTEIN; RHOA GTP-BINDING PROTEIN; SIGNAL TRANSDUCTION;

EID: 84902257083     PISSN: 10624821     EISSN: 14736543     Source Type: Journal    
DOI: 10.1097/01.mnh.0000447018.28852.b6     Document Type: Review

References (115)

1. Pavenstadt H, Kriz W, Kretzler M. Cell biology of the glomerular podocyte. Physiol Rev 2003; 83:253-307.
2. Kestila M, Lenkkeri U, Mannikko M, et al. Positionally cloned gene for a novel glomerular protein - nephrin - is mutated in congenital nephrotic syndrome. Mol Cell 1998; 1:575-582.
3. Li H, Zhu J, Aoudjit L, et al. Rat nephrin modulates cell morphology via the adaptor protein Nck. Biochem Biophys Res Commun 2006; 349:310-316.
4. Verma R, Kovari I, Soofi A, et al. Nephrin ectodomain engagement results in Src kinase activation, nephrin phosphorylation, Nck recruitment, and actin polymerization. J Clin Invest 2006; 116:1346-1359.
5. Jones N, Blasutig IM, Eremina V, et al. Nck adaptor proteins link nephrin to the actin cytoskeleton of kidney podocytes. Nature 2006; 440:818-823.
6. Blasutig IM, New LA, Thanabalasuriar A, et al. Phosphorylated YDXV motifs and Nck SH2/SH3 adaptors act cooperatively to induce actin reorganization. Mol Cell Biol 2008; 28:2035-2046.
7. Venkatareddy M, Cook L, Abuarquob K, et al. Nephrin regulates lamellipodia formation by assembling a protein complex that includes Ship2, filamin and lamellipodin. PLoS One 2011; 6:e28710. doi: 10.1371/journal.pone. 0028710.
8. Zhu J, Attias O, Aoudjit L, et al. P21-Activated kinases regulate actin remodeling in glomerular podocytes. Am J Physiol Renal Physiol 2010; 298:F951-F961.
9. Garg P, Verma R, Nihalani D, et al. Neph1 cooperates with nephrin to transduce a signal that induces actin polymerization. Mol Cell Biol 2007; 27:8698-8712.
10. Huber TB, Hartleben B, Kim J, et al. Nephrin and CD2AP associate with phosphoinositide 3-OH kinase and stimulate AKT-dependent signaling. Mol Cell Biol 2003; 23:4917-4928.
11. Zhu J, Sun N, Aoudjit L, et al. Nephrin mediates actin reorganization via phosphoinositide 3-kinase in podocytes. Kidney Int 2008; 73:556-566.
12. Garg P, Verma R, Cook L, et al. Actin-depolymerizing factor cofilin-1 is necessary in maintaining mature podocyte architecture. J Biol Chem 2010; 285:22676-22688.
13. Harita Y, Kurihara H, Kosako H, et al. Phosphorylation of nephrin triggers Ca2+ signaling by recruitment and activation of phospholipase C-{gamma}1. J Biol Chem 2009; 284:8951-8962.
14. George B, Verma R, Soofi AA, et al. Crk1/2-dependent signaling is necessary for podocyte foot process spreading in mouse models of glomerular disease. J Clin Invest 2012; 122:674-692.
15. George B, Fan Q, Dlugos CP, et al. Crk1/2 and CrkL form a hetero-oligomer and functionally complement each other during podocyte morphogenesis. Kidney Int 2014; doi: 10.1038/ki.2013.556. [Epub ahead of print]
16. Jones N, New LA, Fortino MA, et al. Nck proteins maintain the adult glomerular filtration barrier. J Am Soc Nephrol 2009; 20:1533-1543.
17. New LA, Keyvani Chahi A, Jones N. Direct regulation of nephrin tyrosine phosphorylation by Nck adaptor proteins. J Biol Chem 2013; 288:1500-1510.
18. Tomasevic N, Jia Z, Russell A, et al. Differential regulation of WASP and N-WASP by Cdc42, Rac1, Nck, and PI(4,5)P2. Biochemistry 2007; 46:3494-3502.
19. Rohatgi R, Nollau P, Ho H, et al. Nck and phosphatidylinositol 4,5-bisphosphate synergistically activate actin polymerization through the n-wasp- Arp2/3 pathway. J Biol Chem 2001; 276:26448-26452.
20. Schell C, Baumhakl L, Salou S, et al. N-wasp is required for stabilization of podocyte foot processes. J Am Soc Nephrol 2013; 24:713-721.
21. Buvall L, Rashmi P, Lopez-Rivera E, et al. Proteasomal degradation of Nck1 but not Nck2 regulates RhoA activation and actin dynamics. Nat Commun 2013; 4:2863.
22. Scott RP, Hawley SP, Ruston J, et al. Podocyte-specific loss of Cdc42 leads to congenital nephropathy. J Am Soc Nephrol 2012; 23:1149-1154.
23. Fan X, Li Q, Pisarek-Horowitz A, et al. Inhibitory effects of Robo2 on nephrin: a crosstalk between positive and negative signals regulating podocyte structure. Cell Rep 2012; 2:52-61.
24. Canaud G, Bienaime F, Viau A, et al. AKT2 is essential to maintain podocyte viability and function during chronic kidney disease. Nat Med 2013; 19:1288-1296.
25. Zhang F, Zhao Y, Han Z. An in vivo functional analysis system for renal gene discovery in Drosophila pericardial nephrocytes. J Am Soc Nephrol 2013; 24:191-197.
26. Donoviel DB, Freed DD, Vogel H, et al. Proteinuria and perinatal lethality in mice lacking NEPH1, a novel protein with homology to NEPHRIN. Mol Cell Biol 2001; 21:4829-4836.
27. Wang H, Lehtonen S, Chen YC, et al. Neph3 associates with regulation of glomerular and neural development in zebrafish. Differentiation 2012; 83:38-46.
28. Littman MP, Wiley CA, Raducha MG, Henthorn PS. Glomerulopathy and mutations in NPHS1 and KIRREL2 in soft-coated Wheaten Terrier dogs. Mamm Genome 2013; 24:119-126.
29. Prince JE, Brignall AC, Cutforth T, et al. Kirrel3 is required for the coalescence of vomeronasal sensory neuron axons into glomeruli and for male- male aggression. Development 2013; 140:2398-2408.
30. Volker LA, Petry M, Abdelsabour-Khalaf M, et al. Comparative analysis of Neph gene expression in mouse and chicken development. Histochem Cell Biol 2012; 137:355-366.
31. Mallik L, Arif E, Sharma P, et al. Solution structure analysis of cytoplasmic domain of podocyte protein Neph1 using small/wide angle X-ray scattering (SWAXS). J Biol Chem 2012; 287:9441-9453.
32. Helmstadter M, Luthy K, Godel M, et al. Functional study of mammalian Neph proteins in Drosophila melanogaster. PLoS One 2012; 7:e40300.
33. Arif E, Wagner MC, Johnstone DB, et al. Motor protein Myo1c is a podocyte protein that facilitates the transport of slit diaphragm protein Neph1 to the podocyte membrane. Mol Cell Biol 2011; 31:2134-2150.
34. Bisson N, Ruston J, Jeansson M, et al. The adaptor protein Grb2 is not essential for the establishment of the glomerular filtration barrier. PLoS One 2012; 7:e50996.
35. Schell C, Grahammer F, Huber TB. The slit revisited: analyzing the role of nephrin and the whole Neph family using an in vivo comparative approach. J Am Soc Nephrol 2012; 23:526A. [Abstract]
36. Arif E, Rathore YS, Kumari B, et al. Slit diaphragm protein Neph1 and its signaling: a novel therapeutic target for protection of podocytes against glomerular injury. J Biol Chem 2014; 289:9502-9518.
37. Mouawad F, Tsui H, Takano T. Role of Rho-GTPases and their regulatory proteins in glomerular podocyte function. Can J Physiol Pharmacol 2013; 91:773-782.
38. Sun H, Schlondorff JS, Brown EJ, et al. Rho activation of mDia formins is modulated by an interaction with inverted formin 2 (INF2). Proc Natl Acad Sci USA 2011; 108:2933-2938.
39. Sun H, Schlondorff J, Higgs HN, Pollak MR. Inverted formin 2 regulates actin dynamics by antagonizing Rho/diaphanous-related formin signaling. J Am Soc Nephrol 2013; 24:917-929.
40. Barua M, Brown EJ, Charoonratana VT, et al. Mutations in the INF2 gene account for a significant proportion of familial but not sporadic focal and segmental glomerulosclerosis. Kidney Int 2013; 83:316-322.
41. Brown EJ, Schlondorff JS, Becker DJ, et al. Mutations in the formin gene INF2 cause focal segmental glomerulosclerosis. Nat Genet 2010; 42:72-76.
42. Boyer O, Benoit G, Gribouval O, et al. Mutations in INF2 are a major cause of autosomal dominant focal segmental glomerulosclerosis. J Am Soc Nephrol 2011; 22:239-245.
43. Wang L, Ellis MJ, Gomez JA, et al. Mechanisms of the proteinuria induced by Rho GTPases. Kidney Int 2012; 81:1075-1085.
44. Babelova A, Jansen F, Sander K, et al. Activation of Rac-1 and RhoA contributes to podocyte injury in chronic kidney disease. PLoS One 2013; 8:e80328.
45. Shibata S, Nagase M, Fujita T. Fluvastatin ameliorates podocyte injury in proteinuric rats via modulation of excessive Rho signaling. J Am Soc Nephrol 2006; 17:754-764.
46. Komers R, Oyama TT, Beard DR, et al. Rho kinase inhibition protects kidneys from diabetic nephropathy without reducing blood pressure. Kidney Int 2011; 79:432-442.
47. Faul C, Donnelly M, Merscher-Gomez S, et al. The actin cytoskeleton of kidney podocytes is a direct target of the antiproteinuric effect of cyclosporine A. Nat Med 2008; 14:931-938.
48. Mouawad F, Aoudjit L, Jiang R, et al. Role of guanine nucleotide exchange factor-H1 in complement-mediated RhoA activation in glomerular epithelial cells. J Biol Chem 2013; 289:4206-4218.
49. Zhu L, Jiang R, Aoudjit L, et al. Activation of RhoA in podocytes induces focal segmental glomerulosclerosis. J Am Soc Nephrol 2011; 22:1621-1630.
50. Gee HY, Saisawat P, Ashraf S, et al. ARHGDIA mutations cause nephrotic syndrome via defective RHO GTPase signaling. J Clin Invest 2013; 123:3243-3253.
51. Gupta IR, Baldwin C, Auguste D, et al. ARHGDIA: a novel gene implicated in nephrotic syndrome. J Med Genet 2013; 50:330-338.
52. Akilesh S, Suleiman H, Yu H, et al. Arhgap24 inactivates Rac1 in mouse podocytes, and a mutant form is associated with familial focal segmental glomerulosclerosis. J Clin Invest 2011; 121:4127-4137.
53. Blattner SM, Hodgin JB, Nishio M, et al. Divergent functions of the Rho GTPases Rac1 and Cdc42 in podocyte injury. Kidney Int 2013; 84:920-930.
54. Zhang H, Cybulsky AV, Aoudjit L, et al. Role of Rho-GTPases in complementmediated glomerular epithelial cell injury. Am J Physiol Renal Physiol 2007; 293:F148-F156.
55. Attias O, Jiang R, Aoudjit L, et al. Rac1 contributes to actin organization in glomerular podocytes. Nephron Exp Nephrol 2010; 114:e93-e106.
56. Laurin M, Dumouchel A, Fukui Y, Cote JF. The Rac-specific exchange factors Dock1 and Dock5 are dispensable for the establishment of the glomerular filtration barrier in vivo. Small GTPases 2013; 4:221-230.
57. Yu H, Suleiman H, Kim AH, et al. Rac1 activation in podocytes induces rapid foot process effacement and proteinuria. Mol Cell Biol 2013; 33:4755-4764.
58. Shibata S, Nagase M, Yoshida S, et al. Modification of mineralocorticoid receptor function by Rac1 GTPase: implication in proteinuric kidney disease. Nat Med 2008; 14:1370-1376.
59. Schaldecker T, Kim S, Tarabanis C, et al. Inhibition of the TRPC5 ion channel protects the kidney filter. J Clin Invest 2013; 123:5298-5309.
60. Boyer O, Nevo F, Plaisier E, et al. INF2 mutations in Charcot-Marie-Tooth disease with glomerulopathy. N Engl J Med 2011; 365:2377-2388.
61. Grahammer F, Schell C, Huber TB. The podocyte slit diaphragm - from a thin grey line to a complex signalling hub. Nat Rev Nephrol 2013; 9:587-598.
62. George B, Holzman LB. Signaling from the podocyte intercellular junction to the actin cytoskeleton. Semin Nephrol 2012; 32:307-318.
63. Huber TB, Hartleben B, Winkelmann K, et al. Loss of podocyte aPKClambda/ iota causes polarity defects and nephrotic syndrome. J Am Soc Nephrol 2009; 20:798-806.
64. Hirose T, Satoh D, Kurihara H, et al. An essential role of the universal polarity protein, aPKClambda, on the maintenance of podocyte slit diaphragms. PLoS One 2009; 4:e4194.
65. Hartleben B, Widmeier E, Suhm M, et al. aPKClambda/iota and aPKCzeta contribute to podocyte differentiation and glomerular maturation. J Am Soc Nephrol 2013; 24:253-267.
66. Babayeva S, Rocque B, Aoudjit L, et al. Planar cell polarity pathway regulates nephrin endocytosis in developing podocytes. J Biol Chem 2013; 288: 24035-24048.
67. Soda K, Ishibe S. The function of endocytosis in podocytes. Curr Opin Nephrol Hypertens 2013; 22:432-438.
68. Swiatecka-Urban A. Membrane trafficking in podocyte health and disease. Pediatr Nephrol 2013; 28:1723-1737.
69. Soda K, Balkin DM, Ferguson SM, et al. Role of dynamin, synaptojanin, and endophilin in podocyte foot processes. J Clin Invest 2012; 122:4401-4411.
70. Bechtel W, Helmstadter M, Balica J, et al. Vps34 deficiency reveals the importance of endocytosis for podocyte homeostasis. J Am Soc Nephrol 2013; 24:727-743.
71. Chen J, Chen MX, Fogo AB, et al. mVps34 deletion in podocytes causes glomerulosclerosis by disrupting intracellular vesicle trafficking. J Am Soc Nephrol 2013; 24:198-207.
72. Jin X, Wang W, Mao J, et al. Overexpression of Myo1e in mouse podocytes enhances cellular endocytosis, migration, and adhesion. J Cell Biochem 2014; 115:410-419.
73. Krendel M, Osterweil EK, Mooseker MS. Myosin 1E interacts with synaptojanin- 1 and dynamin and is involved in endocytosis. FEBS Lett 2007; 581:644-650.
74. Chase SE, Encina CV, Stolzenburg LR, et al. Podocyte-specific knockout of myosin 1e disrupts glomerular filtration. Am J Physiol Renal Physiol 2012; 303:F1099-F1106.
75. Mao J, Wang D, Mataleena P, et al. Myo1e impairment results in actin reorganization, podocyte dysfunction, and proteinuria in zebrafish and cultured podocytes. PLoS One 2013; 8:e72750.
76. Quack I,RumpLC,Gerke P, et al. Beta-Arrestin2mediatesnephrin endocytosis and impairs slit diaphragm integrity. PNAS 2006; 103:14110-14115.
77. Qin XS, Tsukaguchi H, Shono A, et al. Phosphorylation of nephrin triggers its internalization by raft-mediated endocytosis. J Am Soc Nephrol 2009; 20:2534-2545.
78. Jeon J, Leibiger I, Moede T, et al. Dynamin-mediated nephrin phosphorylation regulates glucose-stimulated insulin release in pancreatic beta cells. J Biol Chem 2012; 287:28932-28942.
79. Jin J, Sison K, Li C, et al. Soluble FLT1 binds lipid microdomains in podocytes to control cell morphology and glomerular barrier function. Cell 2012; 151:384-399.
80. Quaggin SE, Kreidberg JA. Development of the renal glomerulus: good neighbors and good fences. Development 2008; 135:609-620.
81. Peti-Peterdi J, Burford JL, Hackl MJ. The first decade of using multiphoton microscopy for high-power kidney imaging. Am J Physiol Renal Physiol 2012; 302:F227-F233.
82. Khoury CC, Khayat MF, Yeo TK, et al. Visualizing the mouse podocyte with multiphoton microscopy. Biochem Biophys Res Commun 2012; 427:525-530.
83. Hohne M, Ising C, Hagmann H, et al. Light microscopic visualization of podocyte ultrastructure demonstrates oscillating glomerular contractions. Am J Pathol 2013; 182:332-338.
84. Hackl MJ, Burford JL, Villanueva K, et al. Tracking the fate of glomerular epithelial cells in vivo using serial multiphoton imaging in new mouse models with fluorescent lineage tags. Nat Med 2013; 19:1661-1666.
85. Endlich N, Simon O, Gopferich A, et al. Two-photon microscopy reveals stationary podocytes in living zebrafish larvae. J Am Soc Nephrol 2014; 25:681-686.
86. Verma R, Wharram B, Kovari I, et al. Fyn binds to and phosphorylates the kidney slit diaphragm component nephrin. J Biol Chem 2003; 278:20716-20723.
87. Li H, Lemay S, Aoudjit L, et al. Src-family kinase Fyn phosphorylates the cytoplasmic domain of nephrin and modulates its interaction with podocin. J Am Soc Nephrol 2004; 15:3006-3015.
88. Uchida K, Suzuki K, Iwamoto M, et al. Decreased tyrosine phosphorylation of nephrin in rat and human nephrosis. Kidney Int 2008; 73:926-932.
89. Zhang SY, Kamal M, Dahan K, et al. c-mip Impairs podocyte proximal signaling and induces heavy proteinuria. Sci Signal 2010; 3:ra39.
90. Ohashi T, Uchida K, Asamiya Y, et al. Phosphorylation status of nephrin in human membranous nephropathy. Clin Exp Nephrol 2010; 14:51-55.
91. Boerries M, Grahammer F, Eiselein S, et al. Molecular fingerprinting of the podocyte reveals novel gene and protein regulatory networks. Kidney Int 2013; 83:1052-1064.
92. Ju W, Greene CS, Eichinger F, et al. Defining cell-Type specificity at the transcriptional level in human disease. Genome Res 2013; 23:1862- 1873.
93. Sekulic M, Pichler Sekulic S. A compendium of urinary biomarkers indicative of glomerular podocytopathy. Pathol Res Int 2013; 2013:782395.
94. Wickman L, Afshinnia F, Wang SQ, et al. Urine podocyte mRNAs, proteinuria, and progression in human glomerular diseases. J Am Soc Nephrol 2013; 24:2081-2095.
95. Zhou H, Kajiyama H, Tsuji T, et al. Urinary exosomal Wilms tumor-1 as a potential biomarker for podocyte injury. Am J Physiol Renal Physiol 2013; 305:F553-F559.
96. Lv LL, Cao YH, Pan MM, et al. CD2AP mRNA in urinary exosome as biomarker of kidney disease. Clin Chim Acta 2014; 428:26-31.
97. Warsow G, Endlich N, Schordan E, et al. PodNet, a protein-protein interaction network of the podocyte. Kidney Int 2013; 84:104-115.
98. Sistani L, Rodriguez PQ, Hultenby K, et al. Neuronal proteins are novel components of podocyte major processes and their expression in glomerular crescents supports their role in crescent formation. Kidney Int 2013; 83:63-71.
99. Perisic L, Lal M, Hulkko J, et al. Plekhh2, a novel podocyte protein downregulated in human focal segmental glomerulosclerosis, is involved in matrix adhesion and actin dynamics. Kidney Int 2012; 82:1071-1083.
100. Azeloglu EU, Hardy SV, Eungdamrong NJ, et al. Interconnected network motifs control podocyte morphology and kidney function. Sci Signal 2014; 7:ra12.
101. Long DA, Kolatsi-Joannou M, Price KL, et al. Albuminuria is associated with too few glomeruli and too much testosterone. Kidney Int 2013; 83:1118-1129.
102. Ratelade J, Lavin TA, Muda AO, et al. Maternal environment interacts with modifier genes to influence progression of nephrotic syndrome. J Am Soc Nephrol 2008; 19:1491-1499.
103. Johnstone DB, Ikizler O, Zhang J, Holzman LB. Background strain and the differential susceptibility of podocyte-specific deletion of Myh9 on murine models of experimental glomerulosclerosis and HIV nephropathy. PLoS One 2013; 8:e67839.
104. Baleato RM, Guthrie PL, Gubler MC, et al. Deletion of CD151 results in a strain-dependent glomerular disease due to severe alterations of the glomerular basement membrane. Am J Pathol 2008; 173:927-937.
105. Fahey JR, Katoh H, Malcolm R, Perez AV. The case for genetic monitoring of mice and rats used in biomedical research. Mamm Genome 2013; 24:89-94.
106. Gorham JD, Ranson MS, Smith JC, et al. 1+1=3: Development and validation of a SNP-based algorithm to identify genetic contributions from three distinct inbred mouse strains. J Biomol Tech 2012; 23:136-146.
107. McCloskey DT, Rokosh DG, OConnell TD, et al. Alpha(1)-Adrenoceptor subtypes mediate negative inotropy in myocardium from alpha(1A/C)-knockout and wild type mice. J Mol Cell Cardiol 2002; 34:1007-1017.
108. Pippin JW, Brinkkoetter PT, Cormack-Aboud FC, et al. Inducible rodent models of acquired podocyte diseases. Am J Physiol Renal Physiol 2009; 296:F213-F229.
109. Shimizu M, Khoshnoodi J, Akimoto Y, et al. Expression of galectin-1, a new component of slit diaphragm, is altered in minimal change nephrotic syndrome. Lab Invest 2009; 89:178-195.
110. Clement LC, Avila-Casado C, Mace C, et al. Podocyte-secreted angiopoietin- like-4 mediates proteinuria in glucocorticoid-sensitive nephrotic syndrome. Nat Med 2011; 17:117-122.
111. Ashworth S, Teng B, Kaufeld J, et al. Cofilin-1 inactivation leads to proteinuria - studies in zebrafish, mice and humans. PLoS One 2010; 555:e12626.
112. Yu CC, Fornoni A, Weins A, et al. Abatacept in B7-1-positive proteinuric kidney disease. N Engl J Med 2013; 369:2416-2423.
113. Tanaka E, Asanuma K, Kim E, et al. Notch2 activation ameliorates nephrosis. Nat Commun 2014; 5:3296.
114. Tian X, Kim JJ, Monkley SM, et al. Podocyte-Associated talin1 is critical for glomerular filtration barrier maintenance. J Clin Invest 2014; 124:1098-1113.
115. Schell CB, Kerjaschki D, Reiser J, Huber TB. Is podocyte research at a tipping point? Report from the 9(th) International Podocyte Conference. Kidney Int 2012; 82:1041-1043.