КАНАЛ TRPC6 В ПОДОЦИТАХ ПОЧЕЧНЫХ ГЛОМЕРУЛ
PDF

Ключевые слова

почка
гломерула
подоцит
фокально-сегментарный гломерулосклероз
каналы TRPC
Ca2 - сигнализация

Как цитировать

Михайлова, В. Б., Карпушев, А. В., & Юдина, Ю. С. (2020). КАНАЛ TRPC6 В ПОДОЦИТАХ ПОЧЕЧНЫХ ГЛОМЕРУЛ. Российский физиологический журнал им. И. М. Сеченова, 107(2), 135–153. https://doi.org/10.31857/S0869813921020035

Аннотация

Важнейшим компонентом фильтрационного аппарата почечных гломерул являются специализированные клетки висцерального эпителия – подоциты. Физиологическая функция подоцитов критически зависит от надлежащей регуляции внутриклеточного содержания Ca2+; избыточный вход Ca2+ в клетки может привести к нарушению морфологии клеток, подоцитопатии, апоптозу и последующему повреждению гломерулы в целом. Подоцитопатия является одной из основных характеристик протеинурии и фокально-сегментарного гломерулосклероза. Одним из ключевых белков, ответственных за вход Ca2+ в подоцитах, является ионный канал TRPC6. С момента первого обнаружения мутации в гене, кодирующем TRPC6, внимание научного сообщества сосредоточено на исследовании роли этого ионного канала в возникновении и развитии заболеваний почек. Как усиление, так и снижение функциональной активности TRPC6 сопряжено с проявлением тяжелых нефротических синдромов, ведущих к терминальной стадии хронической болезни почек. В обзоре приведены материалы, касающиеся регуляции активности TRPC6 и роли этого канала в патогенезе гломерулярных заболеваний.

https://doi.org/10.31857/S0869813921020035
PDF

Литература

Weaver D.J., Mitsnefes M. Cardiovascular disease in children and adolescents with chronic kidney disease. Semin. Nephrol. 38(6): 559–569. 2018.

Taal M.W. Chronic kidney disease 10 years on: what have we learned? Curr. Opin. Nephrol. Hypertens. 21(6): 607–611. 2012.

Kiefer M.M., Ryan M.J. Primary care of the patient with chronic kidney disease. Med. Clin. North. Am. 99(5): 935–952. 2015.

Somlo S., Mundel P. Getting a foothold in nephrotic syndrome. Nat. Genet. 24(4): 333–335. 2000.

Kerjaschki D. Caught flat-footed: podocyte damage and the molecular bases of focal glomerulosclerosis. J. Clin. Invest. 108(11): 1583–1587. 2001.

Pena-Polanco J.E., Fried L.F. Established and emerging strategies in the treatment of chronic kidney disease. Semin. Nephrol. 36(4): 331–342. 2016.

Tryggvason K., Wartiovaara J. Molecular basis of glomerular permselectivity. Curr. Opin. Nephrol. Hypertens. 10(4): 543–549. 2001.

Kaplan J.M., Kim S.H., North K.N., Rennke H., Correia L.A., Tong H.Q., Mathis B.J., Rodríguez-Pérez J.C., Allen P.G., Beggs A.H., Pollak M.R. Mutations in ACTN4, encoding α-actinin-4, cause familial focal segmental glomerulosclerosis. Nat. Genet. 24(3): 251–256. 2000.

Fissell W.H., Miner J.H. What is the glomerular ultrafiltration barrier? J. Am. Soc. Nephrol. 29(9): 2262–2264. 2018.

Kerjaschki D. Polycation-induced dislocation of slit diaphragms and formation of cell junctions in rat kidney glomeruli: the effects of low temperature, divalent cations, colchicine, and cytochalasin B. Lab. Invest. 39(5): 430–440. 1978.

Hall G., Wang L., Spurney R.F. TRPC Channels in Proteinuric Kidney Diseases. Cells. 9(1): e44. 2019.

Heeringa S.F., Möller C.C., Du J., Yue L., Hinkes B., Chernin G., Vlangos C.N., Hoyer P.F., Reiser J., Hildebrandt F. A novel TRPC6 mutation that causes childhood FSGS. PLoS One. 4(11): e7771. 2009.

Reiser J., Polu K.R., Moller C.C., Herbert S., Villegas I., Vila‑Casado C., McGee M., Sugimoto H., Brown D., Kalluri R., Mundel P., Smith P.L., Clapham D.E., Pollak M.R. TRPC6 is a glomerular slit diaphragm‑associated channel required for normal renal function. Nat. Genet. 37(7): 739–744. 2005.

Winn M.P., Conlon P.J., Lynn K.L., Farrington M.K., Creazzo T., Hawkins A.F., Daskalakis N., Kwan S.Y., Ebersviller S., Burchette J.L., Pericak‑Vance M.A., Howell D.N., Vance J.M., Rosenberg P.B. A mutation in the TRPC6 cation channel causes familial focal segmental glomerulosclerosis. Science. 308(5729): 1801–1804. 2005.

Montell C., Rubin G.M. Molecular characterization of the Drosophila trp locus: a putative integral membrane protein required for phototransduction. Neuron. 2(4):1313-1323. 1989.

Pavenstädt H., Kriz W., Kretzler M. Cell biology of the glomerular podocyte. Physiol. Rev. 83(1): 253–307. 2003.

Wartiovaara J., Öfverstedt L.-G., Khoshnoodi J., Zhang J.J., Mäkelä E., Sandin S., Ruotsalainen V., Cheng R.H., Jalanko H., Skoglund U., Tryggvason K. Nephrin strands contribute to a porous slit diaphragm scaffold as revealed by electron tomography. J. Clin. Invest. 114(10): 1475–1483. 2004.

Haraldsson B., Nyström J., Deen W.M. Properties of the glomerular barrier and mechanisms of proteinuria. Physiol. Rev. 88(2): 451–487. 2008.

Martin C.E., Jones N. Nephrin signaling in the podocyte: An updated view of signal regulation at the slit diaphragm and beyond. Front. Endocrinol. (Lausanne). 9: 302. 2018.

Reiser J., Kriz W., Kretzler M., Mundel P. The glomerular slit diaphragm is a modified adherens junction. J. Am. Soc. Nephrol. 11(1): 1–8. 2000.

Schnabel E., Anderson J.M., Farquhar M.G. The tight junction protein ZO-1 is concentrated along slit diaphragms of the glomerular epithelium. J. Cell. Biol. 111(3): 1255–1263. 1990.

Ruotsalainen V., Ljungberg P., Wartiovaara J., Lenkkeri U., Kestilä M., Jalanko H., Holmberg C., Tryggvason K. Nephrin is specifically located at the slit diaphragm of glomerular podocytes. Proc. Natl. Acad. Sci. USA. 96(14): 7962–7967. 1999.

Sellin L., Huber T.B., Gerke P., Quack I., Pavenstädt H., Walz G. NEPH1 defines a novel family of podocin interacting proteins. FASEB J. 17(1): 115–117. 2003.

Grahammer F., Wigge C., Schell C., Kretz O., Patrakka J., Schneider S., Klose M., Kind J., Arnold S.J., Habermann A., Bräuniger R., Rinschen M.M., Völker L., Bregenzer A., Rubbenstroth D., Boerries M., Kerjaschki D., Miner J.H., Walz G., Benzing T., Fornoni A., Frangakis A.S., Huber T.B. A flexible, multilayered protein scaffold maintains the slit in between glomerular podocytes. J. CIin. Insight. 1(9): e86177. 2016.

Schwarz K., Simons M., Reiser J., Saleem M.A., Faul C., Kriz W., Shaw A.S., Holzman L.B., Mundel P. Podocin, a raft-associated component of the glomerular slit diaphragm, interacts with CD2AP and nephrin. J. Clin. Invest. 108(11): 1621–1629. 2001.

Kriz W., Shirato I., Nagata M., LeHir M., Lemley K.V. The podocyte's response to stress: the enigma of foot process effacement. Am. J. Physiol. Renal Physiol. 304(4): 333–347. 2013.

Kim Y.H., Goyal M., Kurnit D., Wharram B., Wiggins J., Holzman L., Kershaw D., Wiggins R. Podocyte depletion and glomerulosclerosis have a direct relationship in the PAN-treated rat. Kidney Int. 60(3): 957–968. 2001.

Kriz W., Elger M., Hosser H., Hähnel B., Provoost A., Kränzlin B., Gretz N. How does podocyte damage result in tubular damage? Kidney Blood Press. Res. 22(1–2): 26–36. 1999.

Kriz W., Lemley K.V. A potential role for mechanical forces in the detachment of podocytes and the progression of CKD. J. Am. Soc. Nephrol. 26(2): 258–269. 2015.

Kriz W., Lemley K.V. Potential relevance of shear stress for slit diaphragm and podocyte function. Kidney Int. 91(6): 1283–1286. 2017.

Goel M., Sinkins W.G., Zuo C.D., Estacion M., Schilling W.P. Identification and localization of TRPC channels in the rat kidney. Am. J. Physiol. Renal Physiol. 290(5): 1241–1252. 2006.

Ilatovskaya D.V., Levchenko V., Ryan R.P., Cowley A.W. Jr., Staruschenko A. NSAIDs acutely inhibit TRPC channels in freshly isolated rat glomeruli. Biochem. Biophys. Res. Commun. 408(2): 242–247. 2011.

Ilatovskaya D.V., Staruschenko A. TRPC6 channel as an emerging determinant of the podocyte injury susceptibility in kidney diseases. Am. J. Physiol. Renal Physiol. 309(5): 393-397. 2015.

Tian D., Jacobo S.M., Billing D., Rozkalne A., Gage S.D., Anagnostou T., Pavenstadt H., Hsu H.H., Schlondorff J., Ramos A., Greka A. Antagonistic regulation of actin dynamics and cell motility by TRPC5 and TRPC6 channels. Sci. Signal. 3(145): ra77. 2010.

Huber T.B., Schermer B., Müller R.U., Höhne M., Bartram M., Calixto A., Hagmann H., Reinhardt C., Koos F., Kunzelmann K., Shirokova E., Krautwurst D., Harteneck C., Simons M., Pavenstädt H., Kerjaschki D., Thiele C., Walz G., Chalfie M., Benzing T. Podocin and MEC-2 bind cholesterol to regulate the activity of associated ion channels. Proc. Natl. Acad. Sci. USA. 103(46): 17079–17086. 2006.

Anderson M., Kim E.Y., Hagmann H., Benzing T., Dryer S.E. Opposing effects of podocin on the gating of podocyte TRPC6 channels evoked by membrane stretch or diacylglycerol. Am. J. Physiol. Cell Physiol. 305(3): 276–289. 2013.

Kim E.Y., Choi K.J., Dryer S.E. Nephrin binds to the COOH terminus of a largeconductance Ca2+-activated K+ channel isoform and regulates its expression on the cell surface. Am. J. Physiol. Renal Physiol. 295(1): 235–246. 2008.

Kim E.Y., Anderson M., Wilson C., Hagmann H., Benzing T., Dryer S.E. NOX2 interacts with podocyte TRPC6 channels and contributes to their activation by diacylglycerol: essential role of podocin in formation of this complex. Am. J. Physiol. Cell Physiol. 305(9): 960–971. 2013.

Dryer S.E., Reiser J. TRPC6 channels and their binding partners in podocytes: role in glomerular filtration and pathophysiology. Am. J. Physiol. Renal Physiol. 299(4): 689–701. 2010.

Roselli S., Gribouval O., Boute N., Sich M., Benessy F., Attié T., Gubler M.C., Antignac C. Podocin localizes in the kidney to the slit diaphragm area. Am. J. Pathol. 60(1): 131–139. 2002.

Quick K., Zhao J., Eijkelkamp N., Linley J.E., Rugiero F., Cox J.J., Raouf R., Gringhuis M., Sexton J.E., Abramowitz J., Taylor R., Forge A., Ashmore J., Kirkwood N., Kros C.J., Richardson G.P., Freichel M., Flockerzi V., Birnbaumer L., Wood J.N. TRPC3 and TRPC6 are essential for normal mechanotransduction in subsets of sensory neurons and cochlear hair cells. Open Biol. 2(5): 120068. 2012.

Winn M.P., Conlon P.J., Lynn K.L., Howell D.N., Slotterbeck B.D., Smith A.H., Graham F.L., Bembe M., Quarles L.D., Pericak-Vance M.A., Vance J.M. Linkage of a gene causing familial focal segmental glomerulosclerosis to chromosome 11 and further evidence of genetic heterogeneity. Genomics. 58(2): 113–120. 1999.

Santín S., Ars E., Rossetti S., Salido E., Silva I., García-Maset R., Giménez I., Ruíz P., Mendizábal S., Luciano Nieto J., Peña A., Camacho J.A., Fraga G., Cobo M.A., Bernis C., Ortiz A., de Pablos A.L., Sánchez-Moreno A., Pintos G., Mirapeix E., Fernández-Llama P., Ballarín J., Torra R., Zamora I., López-Hellin J., Madrid A., Ventura C., Vilalta R., Espinosa L., García C., Melgosa M., Navarro M., Giménez A., Cots J.V., Alexandra S., Caramelo C., Egido J., San José M.D., de la Cerda F., Sala P., Raspall F., Vila A., Daza A.M., Vázquez M., Ecija J.L., Espinosa M., Justa M.L., Poveda R., Aparicio C., Rosell J., Muley R., Montenegro J., González D., Hidalgo E., de Frutos D.B., Trillo E., Gracia S., de los Ríos F.J. TRPC6 mutational analysis in a large cohort of patients with focal segmental glomerulosclerosis. Nephrol. Dial. Transplant. 24(10): 3089–3096. 2009.

Zhu B., Chen N., Wang Z.H., Pan X.X., Ren H., Zhang W., Wang W.M. Identification and functional analysis of a novel TRPC6 mutation associated with late onset familial focal segmental glomerulosclerosis in Chinese patients. Mutat. Res. 664(1–2): 84–90. 2009.

Gigante M., Caridi G., Montemurno E., Soccio M., d'Apolito M., Cerullo G., Aucella F., Schirinzi A., Emma F., Massella L., Messina G., De Palo T., Ranieri E., Ghiggeri G.M., Gesualdo L. TRPC6 mutations in children with steroid-resistant nephrotic syndrome and atypical phenotype. Clin. J. Am. Soc. Nephrol. 6(7): 1626–1634. 2011.

Hofstra J.M., Lainez S., van Kuijk W.H., Schoots J., Baltissen M.P., Hoefsloot L.H., Knoers N.V., Berden J.H., Bindels R.J., van der Vlag J., Hoenderop J.G., Wetzels J.F., Nijenhuis T. New TRPC6 gain-of-function mutation in a non-consanguineous Dutch family with late-onset focal segmental glomerulosclerosis. Nephrol. Dial. Transplant. 28(7): 1830–1838. 2013.

Riehle M., Büscher A.K., Gohlke B.O., Kaßmann M., Kolatsi-Joannou M., Bräsen J.H., Nagel M., Becker J.U., Winyard P., Hoyer P.F., Preissner R., Krautwurst D., Gollasch M., Weber S., Harteneck C. TRPC6 G757D loss-of-function mutation associates with FSGS. J. Am. Soc. Nephrol. 27(9): 2771–2783. 2016.

Chiluiza D., Krishna S., Schumacher V.A., Schlondorff J. Gain-of-function mutations in transient receptor potential C6 (TRPC6) activate extracellular signal-regulated kinases 1/2 (ERK1/2). J. Biol. Chem. 288(25): 18407–18420. 2013.

Schlöndorff J., Del Camino D., Carrasquillo R., Lacey V., Pollak M.R. TRPC6 mutations associated with focal segmental glomerulosclerosis cause constitutive activation of NFAT-dependent transcription. Am. J. Physiol. Cell Physiol. 296(3): 558-569. 2009.

Wang Y., Jarad G., Tripathi P., Pan M., Cunningham J., Martin D.R., Liapis H., Miner J.H., Chen F. Activation of NFAT signaling in podocytes causes glomerulosclerosis. J. Am. Soc. Nephrol. 21(10): 1657-1666. 2010.

Kanda S., Harita Y., Shibagaki Y., Sekine T., Igarashi T., Inoue T., Hattori S. Tyrosine phosphorylation-dependent activation of TRPC6 regulated by PLC-γ1 and nephrin: effect of mutations associated with focal segmental glomerulosclerosis. Mol. Biol. Cell. 22(11): 1824–1835. 2011.

Buscher A.K., Kranz B., Buscher R., Hildebrandt F., Dworniczak B., Pennekamp P., Kuwertz-Bröking E., Wingen A.M., John U., Kemper M., Monnens L., Hoyer P.F., Weber S., Konrad M. Immunosuppression and renal outcome in congenital and pediatric steroid-resistant nephrotic syndrome. Clin. J. Am. Soc. Nephrol. 5(11): 2075–2084. 2010.

Obeidova L., Reiterova J., Lnenicka P., Stekrova J., Safrankova H., Kohoutova M., Tesař V. TRPC6 gene variants in Czech adult patients with focal segmental glomerulosclerosis and minimal change disease. Folia. Biol. 58(4): 173–176. 2012.

Mir S., Yavascan O., Berdeli A., Sozeri B. TRPC6 gene variants in Turkish children with steroid-resistant nephrotic syndrome. Nephrol. Dial. Transplant. 27(1): 205–209. 2012.

Barua M., Brown E.J., Charoonratana V.T., Genovese G., Sun H., Pollak M.R. Mutations in the INF2 gene account for a significant proportion of familial but not sporadic focal and segmental glomerulosclerosis. Kidney Int. 83(2): 316–322. 2013.

Santin S., Ars E., Rossett S., Salido E., Silva I., Garcia-Maset R. Giménez I., Ruíz P., Mendizábal S., Luciano Nieto J., Peña A., Camacho J.A., Fraga G., Cobo M.A., Bernis C., Ortiz A., de Pablos A.L., Sánchez-Moreno A., Pintos G., Mirapeix E., Fernández-Llama P., Ballarín J., Torra R., Zamora I., López-Hellin J., Madrid A., Ventura C., Vilalta R., Espinosa L., García C., Melgosa M., Navarro M., Giménez A., Cots J.V., Alexandra S., Caramelo C., Egido J., San José M.D., de la Cerda F., Sala P., Raspall F., Vila A., Daza A.M., Vázquez M., Ecija J.L., Espinosa M., Justa M.L., Poveda R., Aparicio C., Rosell J., Muley R., Montenegro J., González D., Hidalgo E., de Frutos D.B., Trillo E., Gracia S., de los Ríos F.J. TRPC6 mutational analysis in a large cohort of patients with focal segmental glomerulosclerosis. Nephrol. Dial. Transplant. 24(10): 3089–3096. 2009.

Buscher A.K., Konrad M., Nagel M., Witzke O., Kribben A., Hoyer P.F., Weber S. Mutations in podocyte genes are a rare cause of primary FSGS associated with ESRD in adult patients. Clin. Nephrol. 78(1): 47–53. 2012.

Gheissari A., Meamar R., Kheirollahi M., Rouigari M., Dehbashi M., Dehghani L., Abedini A. TRPC6 mutational analysis in Iranian children with focal segmental glomerulosclerosis. Iran J. Kidney Dis. 12(6): 341–349. 2018.

Anderson M., Roshanravan H., Khine J., Dryer S.E. Angiotensin II activation of TRPC6 channels in rat podocytes requires generation of reactive oxygen species. J. Cell. Physiol. 229(4): 434–442. 2014.

Taal M.W., Brenner B.M. Renoprotective benefits of RAS inhibition: from ACEI to angiotensin II antagonists. Kidney Int. 57(5):1803-1817. 2000.

Balla T., Varnai P., Tian Y., Smith R.D. Signaling events activated by angiotensin II receptors: what goes before and after the calcium signals. Endocr Res. 24(3-4): 335-344. 1998.

Hoffmann S., Podlich D., Hähnel B., Kriz W., Gretz N. Angiotensin II type 1 receptor overexpression in podocytes induces glomerulosclerosis in transgenic rats. J. Am. Soc. Nephrol. 15(6):1475-1487. 2004.

Roshanravan H., Dryer S.E. ATP acting through P2Y receptors causes activation of podocyte TRPC6 channels: role of podocin and reactive oxygen species. Am. J. Physiol. Renal Physiol. 306(9): 1088–1097. 2014.

Hofmann T., Obukhov A.G., Schaefer M., Harteneck C., Gudermann T., Schultz G. Direct activation of human TRPC6 and TRPC3 channels by diacylglycerol. Nature. 397(6716): 259–263. 1999.

Bousquet S.M., Monet M., Boulay G. Protein kinase C-dependent phosphorylation of transient receptor potential canonical 6 (TRPC6) on serine 448 causes channel inhibition. J. Biol. Chem. 285(52): 40534–40543. 2010.

Kim E.Y., Anderson M., Dryer S.E. Insulin increases surface expression of TRPC6 channels in podocytes: role of NADPH oxidases and reactive oxygen species. Am. J. Physiol. Renal Physiol. 302(3): 298–307. 2012.

Cayouette S., Lussier M.P., Mathieu E.L., Bousquet S.M., Boulay G. Exocytotic insertion of TRPC6 channel into the plasma membrane upon Gq protein-coupled receptor activation. J. Biol. Chem. 279(8): 7241–7246. 2004.

Roshanravan H., Kim E.Y., Dryer S.E. 20-Hydroxyeicosatetraenoic acid (20-HETE) modulates canonical transient receptor potential-6 (TRPC6) channels in podocytes. Front. Physiol. 7: 351. 2016.

Basora N., Boulay G., Bilodeau L., Rousseau E., Payet M.D. 20-hydroxyeicosatetraenoic acid (20-HETE) activates mouse TRPC6 channels expressed in HEK293 cells. J. Biol. Chem. 278(34): 31709–31716. 2003.

Dryer S.E., Roshanravan H., Kim E.Y. TRPC channels: Regulation, dysregulation and contributions to chronic kidney disease. Biochim. Biophys. Acta. Mol. Basis. Dis. 1865(6): 1041-1066. 2019.

Huber T.B., Simons M., Hartleben B., Sernetz L., Schmidts M., Gundlach E., Saleem M.A., Walz G., Benzing T. Molecular basis of the functional podocin-nephrin complex: mutations in the NPHS2 gene disrupt nephrin targeting to lipid raft microdomains. Hum. Mol. Genet. 12(24): 3397–3405. 2003.

Burnham D.N., Uhlinger D.J., Lambeth J.D. Diradylglycerol synergizes with an anionic amphiphile to activate superoxide generation and phosphorylation of p47phox in a cell-free system from human neutrophils. J. Biol. Chem. 265(29): 17550 –17559. 1990.

Park J.W., Babior B.M. The translocation of respiratory burst oxidase components from cytosol to plasma membrane is regulated by guanine nucleotides and diacylglycerol. J. Biol. Chem. 267(28): 19901–19906. 1992.

Qualliotine-Mann D., Agwu D.E., Ellenburg M.D., McCall C.E., McPhail L.C. Phosphatidic acid and diacylglycerol synergize in a cell-free system for activation of NADPH oxidase from human neutrophils. J. Biol. Chem. 268(32): 23843–23849. 1993.

Tyagi S.R., Neckelmann N., Uhlinger D.J., Burnham D.N., Lambeth J.D. Cell-free translocation of recombinant p47-phox, a component of the neutrophil NADPH oxidase: effects of guanosine 5’-O-(3-thiotriphosphate), diacylglycerol, and an anionic amphiphile. Biochemistry. 31(10): 2765–2774. 1992.

Ogawa N., Kurokawa T., Mori Y. Sensing of redox status by TRP channels. Cell. Calcium. 60(2): 115–122. 2016.

Kozai D., Ogawa N., Mori Y. Redox regulation of transient receptor potential channels. Antioxid. Redox Signal. 21(6): 971–986. 2014.

Samanta A., Kiselar J., Pumroy R.A., Han S., Moiseenkova-Bell V.Y. Structural insights into the molecular mechanism of mouse TRPA1 activation and inhibition. J. Gen. Physiol. 150(5): 751–762. 2018.

Pires P.W., Earley S. Redox regulation of transient receptor potential channels in the endothelium. Microcirculation. 2017 Apr; 24(3): 10.1111/micc.12329.

doi: 10.1111/micc.12329

Bouron A., Chauvet S., Dryer S.E., Rosado J.A. Second messenger-operated calcium entry through TRPC6. Adv. Exp. Med. Biol. 898: 201–249. 2016.

Kim E.Y., Roshanravan H., Dryer S.E. Changes in podocyte TRPC channels evoked by plasma and sera from patients with recurrent FSGS and by putative glomerular permeability factors. Biochim. Biophys. Acta. Mol. basis Dis. 1863(9): 2342–2354. 2017.

Kim E.Y., Hassanzadeh Khayyat N., Dryer S.E. Mechanisms underlying modulation of podocyte TRPC6 channels by suPAR: role of NADPH oxidases and Src family tyrosine kinases. Biochim. Biophys. Acta. Mol. Basis Dis. 1864(10): 3527–3536. 2018.

Patel A., Sharif-Naeini R., Folgering J.R., Bichet D., Duprat F., Honoré E. Canonical TRP channels and mechanotransduction: from physiology to disease states. Pflugers. Arch. 460(3): 571–581. 2010.

Wilson C., Dryer S.E. A mutation in TRPC6 channels abolishes their activation by hypoosmotic stretch but does not affect activation by diacylglycerol or G protein signaling cascades. Am. J. Physiol. Renal Physiol. 306(9): 1018–1025. 2014.

Spassova M.A., Hewavitharana T., Xu W., Soboloff J., Gill D.L. A common mechanism underlies stretch activation and receptor activation of TRPC6 channels. Proc. Natl. Acad. Sci. USA. 103(44): 16586–16591. 2006.

Brenner B.M., Troy J.L., Daugharty T.M. The dynamics of glomerular ultrafiltration in the rat. J. Clin. Invest. 50(8): 1776–1780. 1971.

Endlich N., Endlich K. The challenge and response of podocytes to glomerular hypertension. Semin. Nephrol. 32(4): 327–341. 2012.

Browman D.T., Hoegg M.B., Robbins S.M. The SPFH domain-containing proteins: more than lipid raft markers. Trends Cell. Biol. 17(8): 394–402. 2007.

Relle M., Cash H., Brochhausen C., Strand D., Menke J., Galle P.R., Schwarting A. New perspectives on the renal slit diaphragm protein podocin. Mod. Pathol. 24(8): 1101–1110. 2011.

Moshourab R.A., Wetzel C., Martinez-Salgado C., Lewin G.R. Stomatin-domain protein interactions with acid-sensing ion channels modulate nociceptor mechanosensitivity. J. Physiol. 591(22): 5555–5574. 2013.

O'Hagan R., Chalfie M., Goodman M.B. The MEC-4 DEG/ENaC channel of Caenorhabditis elegans touch receptor neurons transduces mechanical signals. Nat. Neurosci. 8(1): 43–50. 2005.

Price M.P., Thompson R.J., Eshcol J.O., Wemmie J.A., Benson C.J. Stomatin modulates gating of acid-sensing ion channels. J. Biol. Chem. 279(51): 53886–53891. 2004.

Brand J., Smith E.S., Schwefel D., Lapatsina L., Poole K., Omerbašić D., Kozlenkov A., Behlke J., Lewin G.R., Daumke O. A stomatin dimer modulates the activity of acid-sensing ion channels. EMBO J. 31(17): 3635–3646. 2012.

Poole K., Herget R., Lapatsina L., Ngo H.D., Lewin G.R. Tuning Piezo ion channels to detect molecular-scale movements relevant for fine touch. Nat. Commun. 5: 3520. 2014.

Lewis A.H., Grandl J. Mechanical sensitivity of Piezo1 ion channels can be tuned by cellular membrane tension. Elife. 4: e12088. 2015.

Möller C.C., Wei C., Altintas M.M., Li J., Greka A., Ohse T., Pippin J.W., Rastaldi M.P., Wawersik S., Schiavi S., Henger A., Kretzler M., Shankland S. J., Reiser J. Induction of TRPC6 channel in acquired forms of proteinuric kidney disease. J. Am. Soc. Nephrol. 18(1): 29–36. 2007.

Rusnak F., Mertz P. Calcineurin: form and function. Physiol. Rev. 80(4): 1483–1521. 2000.

Klee C.B., Crouch T.H., Krinks M.H. Calcineurin: a calcium- and calmodulinbinding protein of the nervous system. Proc. Natl. Acad. Sci. USA. 76(12): 6270–6273. 1979.

Li H., Rao A., Hogan P.G. Interaction of calcineurin with substrates and targeting proteins. Trends Cell. Biol. 21(2): 91–103. 2011.

Song R., Li J., Zhang J., Wang L., Tong L., Wang P., Yang H., Wei Q., Cai H., Luo J. Peptides derived from transcription factor EB bind to calcineurin at a similar region as the NFAT-type motif. Biochimie. 142: 158–167. 2017.

Macian F. NFAT proteins: key regulators of T-cell development and function. Nat. Rev. Immunol. 5(6): 472–484. 2005.

Müller M.R., Rao A. NFAT, immunity and cancer: a transcription factor comes of age. Nat. Rev. Immunol. 10(9): 645–656. 2010.

Nijenhuis T., Sloan A.J., Hoenderop J.G., Flesche J., van Goor H., Kistler A.D., Bakker M., Bindels R.J., de Boer R.A., Möller C.C., Hamming I., Navis G., Wetzels J.F., Berden J.H., Reiser J., Faul C., van der Vlag J. Angiotensin II contributes to podocyte injury by increasing TRPC6 expression via an NFAT-mediated positive feedback signaling pathway. Am. J. Pathol. 179(4): 1719–1732. 2011.

Ma R., Liu L., Jiang W., Yu Y., Song H. FK506 ameliorates podocyte injury in type 2 diabetic nephropathy by down-regulating TRPC6 and NFAT expression. Int. J. Clin. Exp. Pathol. 8(11): 14063–14074. 2015.

Faul C., Donnelly M., Merscher-Gomez S., Chang Y.H., Franz S., Delfgaauw J., Chang J.M., Choi H.Y., Campbell K.N., Kim K., Reiser J., Mundel P. The actin cytoskeleton of kidney podocytes is a direct target of the antiproteinuric effect of cyclosporine A. Nat. Med. 14(9): 931–938. 2008.

Asanuma K., Yanagida-Asanuma E., Faul C., Tomino Y., Kim K., Mundel P. Synaptopodin orchestrates actin organization and cell motility via regulation of RhoA signaling. Nat. Cell. Biol. 8(5): 485–491. 2006.

Gellermann J., Stefanidis C.J., Mitsioni A., Querfeld U. Successful treatment of steroid-resistant nephrotic syndrome associated with WT1 mutations. Pediatr. Nephrol. 25(7): 1285–1289. 2010.

Malina M., Cinek O., Janda J., Seeman T. Partial remission with cyclosporine A in a patient with nephrotic syndrome due to NPHS2 mutation. Pediatr. Nephrol. 24(10): 2051–2053. 2009.

Yu H., Kistler A., Faridi M.H., Meyer J.O., Tryniszewska B., Mehta D., Yue L., Dryer S.E., Reiser J. Synaptopodin limits TRPC6 podocyte surface expression and attenuates proteinuria. J. Am. Soc. Nephrol. 27(11): 3308–3319. 2016.

Verheijden K.A.T., Sonneveld R., Bakker-van Bebber M., Wetzels J.F.M., van der Vlag J., Nijenhuis T. The calcium-dependent protease calpain-1 links TRPC6 activity to podocyte injury. J. Am. Soc. Nephrol. 29(8): 2099–2109. 2018.

Peltier J., Bellocq A., Perez J., Doublier S., Dubois Y.C., Haymann J.P., Camussi G., Baud L. Calpain activation and secretion promote glomerular injury in experimental glomerulonephritis: evidence from calpastatin-transgenic mice. J. Am. Soc. Nephrol. 17(12): 3415–3423. 2006.

Gough R.E., Goult B.T. The tale of two talins - two isoforms to fine-tune integrin signaling. FEBS Letters. 592(12): 2108–2125. 2018.

Franco S.J., Rodgers M.A., Perrin B.J., Han J., Bennin D.A., Critchley D.R., Huttenlocher A. Calpain-mediated proteolysis of talin regulates adhesion dynamics. Nature. Cell. Biol. 6(10): 977–983. 2004.

Farmer L.K., Rollason R., Whitcomb D.J., Ni L., Goodliff A., Lay A.C., Birnbaumer L., Heesom K.J., Xu S.Z., Saleem M.A., Welsh G.I. TRPC6 binds to and activates calpain, independent of its channel activity, and regulates podocyte cytoskeleton, cell adhesion, and motility. J. Am. Soc. Nephrol. 30(10): 1910–1924. 2019.

Turner J.M., Bauer C., Abramowitz M.K., Melamed M.L., Hostetter T.H. Treatment of chronic kidney disease. Kidney Int. 81(4): 351–362. 2012.

Hogan J., Radhakrishnan J. The treatment of idiopathic focal segmental glomerulosclerosis in adults. Adv. Chronic Kidney Dis. 21(5): 434–441. 2014.

Rosenberg A.Z., Kopp J.B. Focal segmental glomerulosclerosis. Clin. J. Am. Soc. Nephrol. 12(3): 502–517. 2017.

Leca N. Focal segmental glomerulosclerosis recurrence in the renal allograft. Adv. Chronic Kidney Dis. 21(5): 448–452. 2014.

Breyer M.D., Susztak K. The next generation of therapeutics for chronic kidney disease. Nat. Rev. Drug Discov. 15(8): 568–588. 2016.

Qin X., Liu Y., Zhu M., Yang Z. The possible relationship between expressions of TRPC3/5 channels and cognitive changes in rat model of chronic unpredictable stress. Behav. Brain Res. 290: 180–186. 2015.

Liu Y., Liu C., Qin X., Zhu M., Yang Z. The change of spatial cognition ability in depression rat model and the possible association with down-regulated protein expression of TRPC6. Behav. Brain Res. 294: 186–193. 2015.

Bröker-Lai J., Kollewe A., Schindeldecker B., Pohle J., Nguyen Chi V., Mathar I., Guzman R., Schwarz Y., Lai A., Weißgerber P., Schwegler H., Dietrich A., Both M., Sprengel R., Draguhn Köhr G., Fakler B., Flockerzi V., Bruns D., Freichel M. Heteromeric channels formed by TRPC1, TRPC4 and TRPC5 define hippocampal synaptic transmission and working memory. EMBO J. 36(18): 2770–2789. 2017.