International Journal of Nephrology England Journal of Medicine, vol. 354, no. 13, pp. 1387–1401, 2006. [15] J. Oh, J. Reiser, and P. Mundel, “Dynamic (re)organization of the podocyte actin cytoskeleton in the nephrotic syndrome,” Pediatric Nephrology, vol. 19, no. 2, pp. 130–137, 2004. [16] M. M. Lo¨wik, P. J. T. A. Groenen, I. Pronk et al., “Focal segmental glomerulosclerosis in a patient homozygous for a CD2AP mutation,” Kidney International, vol. 72, no. 10, pp. 1198–1203, 2007. [17] S. Yaddanapudi, M. M. Altintas, A. D. Kistler et al., “CD2AP in mouse and human podocytes controls a proteolytic program that regulates cytoskeletal structure and cellular survival,” Journal of Clinical Investigation, vol. 121, no. 10, pp. 3965– 3980, 2011. [18] M. Kestila¨, U. Lenkkeri, M. Ma¨nnikko¨ et al., “Positionally cloned gene for a novel glomerular protein—nephrin—is mutated in congenital nephrotic syndrome,” Molecular Cell, vol. 1, no. 4, pp. 575–582, 1998. [19] B. Hinkes, R. C. Wiggins, R. Gbadegesin et al., “Positional cloning uncovers mutations in PLCE1 responsible for a nephrotic syndrome variant that may be reversible,” Nature Genetics, vol. 38, no. 12, pp. 1397–1405, 2006. [20] N. Boute, O. Gribouval, S. Roselli et al., “NPHS2, encoding the glomerular protein podocin, is mutated in autosomal recessive steroid-resistant nephrotic syndrome,” Nature Genetics, vol. 24, no. 4, pp. 349–354, 2000. [21] M. P. Winn, P. J. Conlon, K. L. Lynn et al., “Medicine: a mutation in the TRPC6 cation channel causes familial focal segmental glomerulosclerosis,” Science, vol. 308, no. 5729, pp. 1801–1804, 2005. [22] J. Reiser, K. R. Polu, C. C. Mo¨ller et al., “TRPC6 is a glomerular slit diaphragm-associated channel required for normal renal function,” Nature Genetics, vol. 37, no. 7, pp. 739–744, 2005. [23] E. J. Brown, J. S. Schlo¨ndorﬀ, D. J. Becker et al., “Mutations in the formin gene INF2 cause focal segmental glomerulosclero- sis,” Nature Genetics, vol. 42, no. 1, pp. 72–76, 2010. [24] C. Mele, P. Iatropoulos, R. Donadelli et al., “MYO1E mutations and childhood familial focal segmental glomerulosclerosis,” New England Journal of Medicine, vol. 365, no. 4, pp. 295–306, 2011. [25] C. Faul, K. Asanuma, E. Yanagida-Asanuma, K. Kim, and P. Mundel, “Actin up: regulation of podocyte structure and function by components of the actin cytoskeleton,” Trends in Cell Biology, vol. 17, no. 9, pp. 428–437, 2007. [26] A. Togawa, J. Miyoshi, H. Ishizaki et al., “Progressive impair- ment of kidneys and reproductive organs in mice lacking Rho GDIα,” Oncogene, vol. 18, no. 39, pp. 5373–5380, 1999. [27] S. Shibata, M. Nagase, S. Yoshida et al., “Modiﬁcation of min- eralocorticoid receptor function by Rac1 GTPase: implication in proteinuric kidney disease,” Nature Medicine, vol. 14, no. 12, pp. 1370–1376, 2008. [28] S. Schmieder, M. Nagai, R. A. Orlando, T. Takeda, and M. G. Farquhar, “Podocalyxin activates RhoA and induces actin reorganization through NHERF1 and Ezrin in MDCK cells,” Journal of the American Society of Nephrology, vol. 15, no. 9, pp. 2289–2298, 2004. [29] M. J. Moeller, A. Sooﬁ, G. S. Braun et al., “Protocadherin FAT1 binds Ena/VASP proteins and is necessary for actin dynamics and cell polarization,” The EMBO Journal, vol. 23, no. 19, pp. 3769–3779, 2004. [30] N. Jones, I. M. Blasutig, V. Eremina et al., “Nck adaptor proteins link nephrin to the actin cytoskeleton of kidney podocytes,” Nature, vol. 440, no. 7085, pp. 818–823, 2006. 5 [31] K. Asanuma, E. Yanagida-Asanuma, C. Faul, Y. Tomino, K. Kim, and P. Mundel, “Synaptopodin orchestrates actin orga- nization and cell motility via regulation of RhoA signalling,” Nature Cell Biology, vol. 8, no. 5, pp. 485–491, 2006. [32] J. S. Schlo¨ndorﬀ and M. R. Pollak, “TRPC6 in glomerular health and disease: what we know and what we believe,” Seminars in Cell and Developmental Biology, vol. 17, no. 6, pp. 667–674, 2006. [33] C. C. Mo¨ller, C. Wei, M. M. Altintas et al., “Induction of TRPC6 channel in acquired forms of proteinuric kidney disease,” Journal of the American Society of Nephrology, vol. 18, no. 1, pp. 29–36, 2007. [34] A. Dietrich, M. M. Y. Schnitzler, M. Gollasch et al., “Increased vascular smooth muscle contractility in TRPC6−/− mice,” Molecular and Cellular Biology, vol. 25, no. 16, pp. 6980–6989, 2005. [35] P. Mundel, H. W. Heid, T. M. Mundel, M. Kru¨ger, J. Reiser, and W. Kriz, “Synaptopodin: an actin-associated protein in telencephalic dendrites and renal podocytes,” Journal of Cell Biology, vol. 139, no. 1, pp. 193–204, 1997. [36] S. F. Heeringa, C. C. Mo¨ller, J. Du et al., “A novel TRPC6 mutation that causes childhood FSGS,” PLoS One, vol. 4, no. 11, article e7771, 2009. [37] T. B. Huber, C. Kwoh, H. Wu et al., “Bigenic mouse models of focal segmental glomerulosclerosis involving pairwise inter- action of CD2AP, Fyn, and synaptopodin,” Journal of Clinical Investigation, vol. 116, no. 5, pp. 1337–1345, 2006. [38] E. Yanagida-Asanuma, K. Asanuma, K. Kim et al., “Syn- aptopodin protects against proteinuria by disrupting Cdc42: IRSp53: Mena signaling complexes in kidney podocytes,” American Journal of Pathology, vol. 171, no. 2, pp. 415–427, 2007. [39] C. Wei, C. C. Mo¨ller, M. M. Altintas et al., “Modiﬁcation of kidney barrier function by the urokinase receptor,” Nature Medicine, vol. 14, no. 1, pp. 55–63, 2008. [40] C. Wei, S. El Hindi, J. Li et al., “Circulating urokinase receptor as a cause of focal segmental glomerulosclerosis,” Nature Medicine, vol. 17, no. 8, pp. 952–960, 2011. [41] F. Blasi and P. Carmeliet, “uPAR: a versatile signalling orchestrator,” Nature Reviews Molecular Cell Biology, vol. 3, no. 12, pp. 932–943, 2002. [42] B. Zhang, S. Xie, W. Shi, and Y. Yang, “Amiloride oﬀ-target eﬀect inhibits podocyte urokinase receptor expression and reduces proteinuria,” Nephrology Dialysis Transplantation, vol. 27, no. 5, pp. 1746–1755, 2012. [43] H. Wu, A. Peisley, I. A. Graef, and G. R. Crabtree, “NFAT signaling and the invention of vertebrates,” Trends in Cell Biology, vol. 17, no. 6, pp. 251–260, 2007. [44] A. Rao, “Signaling to gene expression: calcium, calcineurin and NFAT,” Nature Immunology, vol. 10, no. 1, pp. 3–5, 2009. [45] G. R. Crabtree, “Calcium, calcineurin, and the control of transcription,” Journal of Biological Chemistry, vol. 276, no. 4, pp. 2313–2316, 2001. [46] I. A. Graef, F. Chen, and G. R. Crabtree, “NFAT signaling in vertebrate development,” Current Opinion in Genetics and Development, vol. 11, no. 5, pp. 505–512, 2001. [47] G. R. Crabtree and E. N. Olson, “NFAT signaling: chore- ographing the social lives of cells,” Cell, vol. 109, no. 2, pp. S67–S79, 2002. [48] J. Reiser, J. Oh, I. Shirato et al., “Podocyte migration during nephrotic syndrome requires a coordinated interplay between cathepsin L and α3 integrin,” Journal of Biological Chemistry, vol. 279, no. 33, pp. 34827–34832, 2004.