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Annual Review of Physiology

Volume 79, 2017

Receptor-Mediated Endocytosis in the Proximal Tubule

Abstract

Cells lining the proximal tubule (PT) of the kidney are highly specialized for apical endocytosis of filtered proteins and small bioactive molecules from the glomerular ultrafiltrate to maintain essentially protein-free urine. Compromise of this pathway results in low molecular weight (LMW) proteinuria that can progress to end-stage kidney disease. This review describes our current understanding of the endocytic pathway and the multiligand receptors that mediate LMW protein uptake in PT cells, how these are regulated in response to physiologic cues, and the molecular basis of inherited diseases characterized by LMW proteinuria.

Keyword(s): albumin, apical, cubilin, cystinosis, Dent disease, kidney, Lowe syndrome, megalin, proteinuria
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2017-02-10
2025-06-13
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Literature Cited

  1. Vinge L, Lees GE, Nielsen R, Kashtan CE, Bahr A, Christensen EI. 1.  2010. The effect of progressive glomerular disease on megalin-mediated endocytosis in the kidney. Nephrol. Dial. Transpl. 25:2458–67 [Google Scholar]
  2. Moestrup SK, Verroust PJ. 2.  2001. Megalin- and cubilin-mediated endocytosis of protein-bound vitamins, lipids, and hormones in polarized epithelia. Annu. Rev. Nutr. 21:407–28 [Google Scholar]
  3. Kerjaschki D, Farquhar MG. 3.  1982. The pathogenic antigen of Heymann nephritis is a membrane glycoprotein of the renal proximal tubule brush border. PNAS 795557–61 [Google Scholar]
  4. Ozawa M, Yonezawa S, Sato E, Muramatsu T. 4.  1982. A new glycoprotein antigen common to teratocarcinoma, visceral endoderm, and renal tubular brush border. Dev. Biol. 91351–59 [Google Scholar]
  5. Farquhar MG, Saito A, Kerjaschki D, Orlando RA. 5.  1995. The Heymann nephritis antigenic complex: megalin (gp330) and RAP. J. Am. Soc. Nephrol. 635–47 [Google Scholar]
  6. Saito A, Pietromonaco S, Loo AK, Farquhar MG. 6.  1994. Complete cloning and sequencing of rat gp330/“megalin,” a distinctive member of the low density lipoprotein receptor gene family. PNAS 919725–9 [Google Scholar]
  7. Hjälm G, Murray E, Crumley G, Harazim W, Lundgren S. 7.  et al. 1996. Cloning and sequencing of human gp330, a Ca2+-binding receptor with potential intracellular signaling properties. Eur. J. Biochem. 239:132–37 [Google Scholar]
  8. Jeon H, Blacklow SC. 8.  2005. Structure and physiologic function of the low-density lipoprotein receptor. Annu. Rev. Biochem. 74535–62 [Google Scholar]
  9. Takeda T, Yamazaki H, Farquhar MG. 9.  2003. Identification of an apical sorting determinant in the cytoplasmic tail of megalin. Am. J. Physiol. Cell Physiol. 284:C1105–13 [Google Scholar]
  10. Bachinsky DR, Zheng G, Niles JL, McLaughlin M, Abbate M. 10.  et al. 1993. Detection of two forms of GP330. Their role in Heymann nephritis. Am. J. Pathol. 143:598–611 [Google Scholar]
  11. Zou Z, Chung B, Nguyen T, Mentone S, Thomson B, Biemesderfer D. 11.  2004. Linking receptor-mediated endocytosis and cell signaling: evidence for regulated intramembrane proteolysis of megalin in proximal tubule. J. Biol. Chem. 279:34302–10 [Google Scholar]
  12. Christ A, Terryn S, Schmidt V, Christensen EI, Huska MR. 12.  et al. 2010. The soluble intracellular domain of megalin does not affect renal proximal tubular function in vivo. Kidney Int. 78473–77 [Google Scholar]
  13. Li Y, Cong R, Biemesderfer D. 13.  2008. The COOH terminus of megalin regulates gene expression in opossum kidney proximal tubule cells. Am. J. Physiol. Cell Physiol. 295:C529–37 [Google Scholar]
  14. Birn H, Vorum H, Verroust PJ, Moestrup SK, Christensen EI. 14.  2000. Receptor-associated protein is important for normal processing of megalin in kidney proximal tubules. J. Am. Soc. Nephrol. 11:191–202 [Google Scholar]
  15. Willnow TE, Rohlmann A, Horton J, Otani H, Braun JR. 15.  et al. 1996. RAP, a specialized chaperone, prevents ligand-induced ER retention and degradation of LDL receptor-related endocytic receptors. EMBO J. 15:2632–39 [Google Scholar]
  16. Czekay RP, Orlando RA, Woodward L, Lundstrom M, Farquhar MG. 16.  1997. Endocytic trafficking of megalin/RAP complexes: dissociation of the complexes in late endosomes. Mol. Biol. Cell 8517–32 [Google Scholar]
  17. Christensen EI, Birn H, Storm T, Weyer K, Nielsen R. 17.  2012. Endocytic receptors in the renal proximal tubule. Physiology 27:223–36 [Google Scholar]
  18. Leheste JR, Rolinski B, Vorum H, Hilpert J, Nykjaer A. 18.  et al. 1999. Megalin knockout mice as an animal model of low molecular weight proteinuria. Am. J. Pathol. 155:1361–70 [Google Scholar]
  19. Cui S, Verroust PJ, Moestrup SK, Christensen EI. 19.  1996. Megalin/gp330 mediates uptake of albumin in renal proximal tubule. Am. J. Physiol. 271:F900–7 [Google Scholar]
  20. Nielsen R, Courtoy PJ, Jacobsen C, Dom G, Lima WR. 20.  et al. 2007. Endocytosis provides a major alternative pathway for lysosomal biogenesis in kidney proximal tubular cells. PNAS 104:5407–12 [Google Scholar]
  21. Seetharam B, Alpers DH, Allen RH. 21.  1981. Isolation and characterization of the ileal receptor for intrinsic factor-cobalamin. J. Biol. Chem. 256:3785–90 [Google Scholar]
  22. Seetharam B, Christensen EI, Moestrup SK, Hammond TG, Verroust PJ. 22.  1997. Identification of rat yolk sac target protein of teratogenic antibodies, gp280, as intrinsic factor-cobalamin receptor. J. Clin. Investig. 992317–22 [Google Scholar]
  23. Sahali D, Mulliez N, Chatelet F, Dupuis R, Ronco P, Verroust P. 23.  1988. Characterization of a 280-kD protein restricted to the coated pits of the renal brush border and the epithelial cells of the yolk sac. Teratogenic effect of the specific monoclonal antibodies. J. Exp. Med. 167:213–18 [Google Scholar]
  24. Moestrup SK, Kozyraki R, Kristiansen M, Kaysen JH, Rasmussen HH. 24.  et al. 1998. The intrinsic factor-vitamin B12 receptor and target of teratogenic antibodies is a megalin-binding peripheral membrane protein with homology to developmental proteins. J. Biol. Chem. 273:5235–42 [Google Scholar]
  25. Amsellem S, Gburek J, Hamard G, Nielsen R, Willnow TE. 25.  et al. 2010. Cubilin is essential for albumin reabsorption in the renal proximal tubule. J. Am. Soc. Nephrol. 21:1859–67 [Google Scholar]
  26. Kozyraki R, Fyfe J, Verroust PJ, Jacobsen C, Dautry-Varsat A. 26.  et al. 2001. Megalin-dependent cubilin-mediated endocytosis is a major pathway for the apical uptake of transferrin in polarized epithelia. PNAS 9812491–96 [Google Scholar]
  27. Strope S, Rivi R, Metzger T, Manova K, Lacy E. 27.  2004. Mouse amnionless, which is required for primitive streak assembly, mediates cell-surface localization and endocytic function of cubilin on visceral endoderm and kidney proximal tubules. Development 131:4787–95 [Google Scholar]
  28. He Q, Madsen M, Kilkenney A, Gregory B, Christensen EI. 28.  et al. 2005. Amnionless function is required for cubilin brush-border expression and intrinsic factor-cobalamin (vitamin B12) absorption in vivo. Blood 106:1447–53 [Google Scholar]
  29. Ahuja R, Yammani R, Bauer JA, Kalra S, Seetharam S, Seetharam B. 29.  2008. Interactions of cubilin with megalin and the product of the amnionless gene (AMN): effect on its stability. Biochem. J. 410:301–8 [Google Scholar]
  30. Anderson CL, Chaudhury C, Kim J, Bronson CL, Wani MA, Mohanty S. 30.  2006. Perspective—FcRn transports albumin: relevance to immunology and medicine. Trends Immunol. 27:343–48 [Google Scholar]
  31. Chaudhury C, Mehnaz S, Robinson JM, Hayton WL, Pearl DK. 31.  et al. 2003. The major histocompatibility complex-related Fc receptor for IgG (FcRn) binds albumin and prolongs its lifespan. J. Exp. Med. 197:315–22 [Google Scholar]
  32. Akilesh S, Huber TB, Wu H, Wang G, Hartleben B. 32.  et al. 2008. Podocytes use FcRn to clear IgG from the glomerular basement membrane. PNAS 105:967–72 [Google Scholar]
  33. Tenten V, Menzel S, Kunter U, Sicking EM, van Roeyen CR. 33.  et al. 2013. Albumin is recycled from the primary urine by tubular transcytosis. J. Am. Soc. Nephrol. 24:1966–80 [Google Scholar]
  34. Gekle M. 34.  2007. Renal albumin handling: a look at the dark side of the filter. Kidney Int. 71479–81 [Google Scholar]
  35. Park CH, Maack T. 35.  1984. Albumin absorption and catabolism by isolated perfused proximal convoluted tubules of the rabbit. J. Clin. Investig. 73767–77 [Google Scholar]
  36. Gudehithlu KP, Pegoraro AA, Dunea G, Arruda JA, Singh AK. 36.  2004. Degradation of albumin by the renal proximal tubule cells and the subsequent fate of its fragments. Kidney Int 652113–22 [Google Scholar]
  37. Hatae T, Fujita M, Sagara H, Okuyama K. 37.  1986. Formation of apical tubules from large endocytic vacuoles in kidney proximal tubule cells during absorption of horseradish peroxidase. Cell Tissue Res. 246:271–78 [Google Scholar]
  38. Rabito CA. 38.  1983. Phosphate uptake by a kidney cell line (LLC-PK1). Am. J. Physiol. 245:F22–31 [Google Scholar]
  39. Ryan MJ, Johnson G, Kirk J, Fuerstenberg SM, Zager RA, Torok-Storb B. 39.  1994. HK-2: An immortalized proximal tubule epithelial cell line from normal adult human kidney. Kidney Int. 4548–57 [Google Scholar]
  40. Mattila PE, Raghavan V, Rbaibi Y, Baty CJ, Weisz OA. 40.  2013. Rab11a-positive compartments in proximal tubule cells sort fluid phase and membrane cargo. Am. J. Physiol. Cell Physiol. 306:C441–49 [Google Scholar]
  41. Shmuel M, Nodel-Berner E, Hyman T, Rouvinski A, Altschuler Y. 41.  2007. Caveolin 2 regulates endocytosis and trafficking of the M1 muscarinic receptor in MDCK epithelial cells. Mol. Biol. Cell 18:1570–85 [Google Scholar]
  42. Zhuang Z, Marshansky V, Breton S, Brown D. 42.  2011. Is caveolin involved in normal proximal tubule function? Presence in model PT systems but absence in situ. Am. J. Physiol. Renal Physiol. 300F199–206 [Google Scholar]
  43. Costa SR, Okamoto CT, Hamm-Alvarez SF. 43.  da 2003. Actin microfilaments et al.—the many components, effectors and regulators of epithelial cell endocytosis. Adv. Drug Deliv. Rev. 551359–83 [Google Scholar]
  44. Grant BD, Donaldson JG. 44.  2009. Pathways and mechanisms of endocytic recycling. Nat. Rev. Mol. Cell. Biol. 10:597–608 [Google Scholar]
  45. Huotari J, Helenius A. 45.  2011. Endosome maturation. EMBO J. 303481–500 [Google Scholar]
  46. Sheff DR, Daro EA, Hull M, Mellman I. 46.  1999. The receptor recycling pathway contains two distinct populations of early endosomes with different sorting functions. J. Cell Biol. 145:123–39 [Google Scholar]
  47. Wang E, Brown PS, Aroeti B, Chapin SJ, Mostov KE, Dunn KW. 47.  2000. Apical and basolateral endocytic pathways of MDCK cells meet in acidic common endosomes distinct from a nearly-neutral apical recycling endosome. Traffic 1480–93 [Google Scholar]
  48. Cramm-Behrens CI, Dienst M, Jacob R. 48.  2008. Apical cargo traverses endosomal compartments on the passage to the cell surface. Traffic 92206–20 [Google Scholar]
  49. Ang AL, Folsch H, Koivisto UM, Pypaert M, Mellman I. 49.  2003. The Rab8 GTPase selectively regulates AP-1B-dependent basolateral transport in polarized Madin-Darby canine kidney cells. J. Cell Biol. 163:339–50 [Google Scholar]
  50. Ang AL, Taguchi T, Francis S, Fölsch H, Murrells LJ. 50.  et al. 2004. Recycling endosomes can serve as intermediates during transport from the Golgi to the plasma membrane of MDCK cells. J. Cell Biol. 167:531–43 [Google Scholar]
  51. Sato T, Mushiake S, Kato Y, Sato K, Sato M. 51.  et al. 2007. The Rab8 GTPase regulates apical protein localization in intestinal cells. Nature 448366–69 [Google Scholar]
  52. Huber LA, Pimplikar S, Parton RG, Virta H, Zerial M, Simons K. 52.  1993. Rab8, a small GTPase involved in vesicular traffic between the TGN and the basolateral plasma membrane. J. Cell Biol. 123:35–45 [Google Scholar]
  53. Knodler A, Feng S, Zhang J, Zhang X, Das A. 53.  et al. 2010. Coordination of Rab8 and Rab11 in primary ciliogenesis. PNAS 107:6346–51 [Google Scholar]
  54. Kitt KN, Hernandez-Deviez D, Ballantyne SD, Spiliotis ET, Casanova JE, Wilson JM. 54.  2008. Rab14 regulates apical targeting in polarized epithelial cells. Traffic 91218–31 [Google Scholar]
  55. McCarter SD, Johnson DL, Kitt KN, Donohue C, Adams A, Wilson JM. 55.  2010. Regulation of tight junction assembly and epithelial polarity by a resident protein of apical endosomes. Traffic 11:856–66 [Google Scholar]
  56. Su H, Liu B, Frohlich O, Ma H, Sands JM, Chen G. 56.  2013. Small GTPase Rab14 down-regulates UT-A1 urea transport activity through enhanced clathrin-dependent endocytosis. FASEB J. 27:4100–7 [Google Scholar]
  57. Rodman JS, Seidman L, Farquhar MG. 57.  1986. The membrane composition of coated pits, microvilli, endosomes, and lysosomes is distinctive in the rat kidney proximal tubule cell. J. Cell Biol. 102:77–87 [Google Scholar]
  58. Nielsen S. 58.  1993. Endocytosis in proximal tubule cells involves a two-phase membrane-recycling pathway. Am. J. Physiol. 264:C823–35 [Google Scholar]
  59. Rodman JS, Kerjaschki D, Merisko E, Farquhar MG. 59.  1984. Presence of an extensive clathrin coat on the apical plasmalemma of the rat kidney proximal tubule cell. J. Cell Biol. 981630–36 [Google Scholar]
  60. Birn H, Christensen EI, Nielsen S. 60.  1993. Kinetics of endocytosis in renal proximal tubule studied with ruthenium red as membrane marker. Am. J. Physiol. 264:F239–50 [Google Scholar]
  61. Gekle M, Mildenberger S, Freudinger R, Schwerdt G, Silbernagl S. 61.  1997. Albumin endocytosis in OK cells: dependence on actin and microtubules and regulation by protein kinases. Am. J. Physiol. 272:F668–77 [Google Scholar]
  62. Zhai XY, Nielsen R, Birn H, Drumm K, Mildenberger S. 62.  et al. 2000. Cubilin- and megalin-mediated uptake of albumin in cultured proximal tubule cells of opossum kidney. Kidney Int. 581523–33 [Google Scholar]
  63. Raghavan V, Rbaibi Y, Pastor-Soler NM, Carattino MD, Weisz OA. 63.  2014. Shear stress-dependent regulation of apical endocytosis in renal proximal tubule cells mediated by primary cilia. PNAS 111:8506–11 [Google Scholar]
  64. Decorti G, Malusa N, Furlan G, Candussio L, Klugmann FB. 64.  1999. Endocytosis of gentamicin in a proximal tubular renal cell line. Life Sci. 651115–24 [Google Scholar]
  65. Lui EC, Bendayan R. 65.  1998. Gentamicin uptake by LLCPK1 cells: effect of intracellular and extracellular pH changes. Can. J. Physiol. Pharmacol. 76155–60 [Google Scholar]
  66. Oleinikov AV, Zhao J, Makker SP. 66.  2000. Cytosolic adaptor protein Dab2 is an intracellular ligand of endocytic receptor gp600/megalin. Biochem. J. 347Pt. 3613–21 [Google Scholar]
  67. Pedersen GA, Chakraborty S, Steinhauser AL, Traub LM, Madsen M. 67.  2010. AMN directs endocytosis of the intrinsic factor-vitamin B(12) receptor cubam by engaging ARH or Dab2. Traffic 11:706–20 [Google Scholar]
  68. Wilund KR, Yi M, Campagna F, Arca M, Zuliani G. 68.  et al. 2002. Molecular mechanisms of autosomal recessive hypercholesterolemia. Hum. Mol. Genet. 11:3019–30 [Google Scholar]
  69. Fang L, Garuti R, Kim BY, Wade JB, Welling PA. 69.  2009. The ARH adaptor protein regulates endocytosis of the ROMK potassium secretory channel in mouse kidney. J. Clin. Investig. 119:3278–89 [Google Scholar]
  70. Hatae T, Ichimura T, Ishida T, Sakurai T. 70.  1997. Apical tubular network in the rat kidney proximal tubule cells studied by thick-section and scanning electron microscopy. Cell Tissue Res. 288:317–25 [Google Scholar]
  71. Nagai M, Meerloo T, Takeda T, Farquhar MG. 71.  2003. The adaptor protein ARH escorts megalin to and through endosomes. Mol. Biol. Cell 14:4984–96 [Google Scholar]
  72. Anzenberger U, Bit-Avragim N, Rohr S, Rudolph F, Dehmel B. 72.  et al. 2006. Elucidation of megalin/LRP2-dependent endocytic transport processes in the larval zebrafish pronephros. J. Cell Sci. 119:2127–37 [Google Scholar]
  73. Hurtado-Lorenzo A, Skinner M. Annan J, Futai M, Sun-Wada GH. 73. , El et al. 2006. V-ATPase interacts with ARNO and Arf6 in early endosomes and regulates the protein degradative pathway. Nat. Cell Biol. 8124–36 [Google Scholar]
  74. Gekle M, Volker K, Mildenberger S, Freudinger R, Shull GE, Wiemann M. 74.  2004. NHE3 Na+/H+ exchanger supports proximal tubular protein reabsorption in vivo. Am. J. Physiol. Renal Physiol. 287:F469–73 [Google Scholar]
  75. Scheel O, Zdebik AA, Lourdel S, Jentsch TJ. 75.  2005. Voltage-dependent electrogenic chloride/proton exchange by endosomal CLC proteins. Nature 436424–27 [Google Scholar]
  76. Schmidt MM, Townson SA, Andreucci AJ, King BM, Schirmer EB. 76.  et al. 2013. Crystal structure of an HSA/FcRn complex reveals recycling by competitive mimicry of HSA ligands at a pH-dependent hydrophobic interface. Structure 21:1966–78 [Google Scholar]
  77. Rangel-Filho A, Lazar J, Moreno C, Geurts A, Jacob HJ. 77.  2013. Rab38 modulates proteinuria in model of hypertension-associated renal disease. J. Am. Soc. Nephrol. 24:283–92 [Google Scholar]
  78. Schwegler JS, Heppelmann B, Mildenberger S, Silbernagl S. 78.  1991. Receptor-mediated endocytosis of albumin in cultured opossum kidney cells: a model for proximal tubular protein reabsorption. Pflugers Arch. 418:383–92 [Google Scholar]
  79. Gotoh N, Yan Q, Du Z, Biemesderfer D, Kashgarian M. 79.  et al. 2010. Altered renal proximal tubular endocytosis and histology in mice lacking myosin-VI. Cytoskeleton 67178–92 [Google Scholar]
  80. Hosaka K, Takeda T, Iino N, Hosojima M, Sato H. 80.  et al. 2009. Megalin and nonmuscle myosin heavy chain IIA interact with the adaptor protein Disabled-2 in proximal tubule cells. Kidney Int. 751308–15 [Google Scholar]
  81. Thelen S, Abouhamed M, Ciarimboli G, Edemir B, Bahler M. 81.  2015. Rho GAP myosin IXa is a regulator of kidney tubule function. Am. J. Physiol. Renal Physiol. 309F501–13 [Google Scholar]
  82. Dance AL, Miller M, Seragaki S, Aryal P, White B. 82.  et al. 2004. Regulation of myosin-VI targeting to endocytic compartments. Traffic 5798–813 [Google Scholar]
  83. Elkjaer ML, Birn H, Agre P, Christensen EI, Nielsen S. 83.  1995. Effects of microtubule disruption on endocytosis, membrane recycling and polarized distribution of Aquaporin-1 and gp330 in proximal tubule cells. Eur. J. Cell Biol. 6757–72 [Google Scholar]
  84. Reed AA, Loh NY, Terryn S, Lippiat JD, Partridge C. 84.  et al. 2010. CLC-5 and KIF3B interact to facilitate CLC-5 plasma membrane expression, endocytosis, and microtubular transport: relevance to pathophysiology of Dent's disease. Am. J. Physiol. Renal Physiol. 298:F365–80 [Google Scholar]
  85. Hryciw DH, Wang Y, Devuyst O, Pollock CA, Poronnik P, Guggino WB. 85.  2003. Cofilin interacts with ClC-5 and regulates albumin uptake in proximal tubule cell lines. J. Biol. Chem. 278:40169–76 [Google Scholar]
  86. Dachy A, Paquot F, Debray G, Bovy C, Christensen EI. 86.  et al. 2015. In-depth phenotyping of a Donnai-Barrow patient helps clarify proximal tubule dysfunction. Pediatr. Nephrol. 301027–31 [Google Scholar]
  87. Kur E, Christa A, Veth KN, Gajera CR, Andrade-Navarro MA. 87.  et al. 2011. Loss of Lrp2 in zebrafish disrupts pronephric tubular clearance but not forebrain development. Dev. Dyn. 240:1567–77 [Google Scholar]
  88. Christensen EI, Devuyst O, Dom G, Nielsen R, Van der Smissen P. 88.  et al. 2003. Loss of chloride channel ClC-5 impairs endocytosis by defective trafficking of megalin and cubilin in kidney proximal tubules. PNAS 100:8472–77 [Google Scholar]
  89. Moulin P, Igarashi T, Van der Smissen P, Cosyns JP, Verroust P. 89.  et al. 2003. Altered polarity and expression of H+-ATPase without ultrastructural changes in kidneys of Dent's disease patients. Kidney Int. 631285–95 [Google Scholar]
  90. Wang SS, Devuyst O, Courtoy PJ, Wang XT, Wang H. 90.  et al. 2000. Mice lacking renal chloride channel, CLC-5, are a model for Dent's disease, a nephrolithiasis disorder associated with defective receptor-mediated endocytosis. Hum. Mol. Genet. 92937–45 [Google Scholar]
  91. Chou SY, Hsu KS, Otsu W, Hsu YC, Luo YC. 91.  et al. 2016. CLIC4 regulates apical exocytosis and renal tube luminogenesis through retromer- and actin-mediated endocytic trafficking. Nat. Commun. 710412 [Google Scholar]
  92. Morris SM, Tallquist MD, Rock CO, Cooper JA. 92.  2002. Dual roles for the Dab2 adaptor protein in embryonic development and kidney transport. EMBO J. 21:1555–64 [Google Scholar]
  93. Nagai J, Christensen EI, Morris SM, Willnow TE, Cooper JA, Nielsen R. 93.  2005. Mutually dependent localization of megalin and Dab2 in the renal proximal tubule. Am. J. Physiol. Renal Physiol. 289:F569–76 [Google Scholar]
  94. Koral K, Li H, Ganesh N, Birnbaum MJ, Hallows KR, Erkan E. 94.  2014. Akt recruits Dab2 to albumin endocytosis in the proximal tubule. Am. J. Physiol. Renal Physiol. 307F1380–89 [Google Scholar]
  95. Koral K, Erkan E. 95.  2012. PKB/Akt partners with Dab2 in albumin endocytosis. Am. J. Physiol. Renal Physiol. 302F1013–24 [Google Scholar]
  96. Caruso-Neves C, Kwon SH, Guggino WB. 96.  2005. Albumin endocytosis in proximal tubule cells is modulated by angiotensin II through an AT2 receptor-mediated protein kinase B activation. PNAS 102:17513–18 [Google Scholar]
  97. Carpentier S, N'Kuli F, Grieco G, Van Der Smissen P, Janssens V. 97.  et al. 2013. Class III phosphoinositide 3-kinase/VPS34 and dynamin are critical for apical endocytic recycling. Traffic 14:933–48 [Google Scholar]
  98. Brunskill NJ, Stuart J, Tobin AB, Walls J, Nahorski S. 98.  1998. Receptor-mediated endocytosis of albumin by kidney proximal tubule cells is regulated by phosphatidylinositide 3-kinase. J. Clin. Investig. 101:2140–50 [Google Scholar]
  99. Hosojima M, Sato H, Yamamoto K, Kaseda R, Soma T. 99.  et al. 2009. Regulation of megalin expression in cultured proximal tubule cells by angiotensin II type 1A receptor- and insulin-mediated signaling cross talk. Endocrinology 150:871–78 [Google Scholar]
  100. Takeyama A, Sato H, Soma-Nagae T, Kabasawa H, Suzuki A. 100.  et al. 2011. Megalin is downregulated via LPS-TNF-α-ERK1/2 signaling pathway in proximal tubule cells. Biochem. Biophys. Res. Commun. 407108–12 [Google Scholar]
  101. Ruggiero C, Elks CM, Kruger C, Cleland E, Addison K. 101.  et al. 2014. Albumin-bound fatty acids but not albumin itself alter redox balance in tubular epithelial cells and induce a peroxide-mediated redox-sensitive apoptosis. Am. J. Physiol. Renal Physiol. 306F896–906 [Google Scholar]
  102. Caruso-Neves C, Pinheiro AA, Cai H, Souza-Menezes J, Guggino WB. 102.  2006. PKB and megalin determine the survival or death of renal proximal tubule cells. PNAS 103:18810–15 [Google Scholar]
  103. Gekle M, Mildenberger S, Freudinger R, Silbernagl S. 103.  1998. Long-term protein exposure reduces albumin binding and uptake in proximal tubule-derived opossum kidney cells. J. Am. Soc. Nephrol. 9960–68 [Google Scholar]
  104. Diwakar R, Pearson AL, Colville-Nash P, Baines DL, Dockrell ME. 104.  2008. Role played by Disabled-2 in albumin induced MAP Kinase signalling. Biochem. Biophys. Res. Commun. 366675–80 [Google Scholar]
  105. Slattery C, Jang Y, Kruger WA, Hryciw DH, Lee A, Poronnik P. 105.  2013. γ-Secretase inhibition promotes fibrotic effects of albumin in proximal tubular epithelial cells. Br. J. Pharmacol. 169:1239–51 [Google Scholar]
  106. Gekle M, Knaus P, Nielsen R, Mildenberger S, Freudinger R. 106.  et al. 2003. Transforming growth factor-beta1 reduces megalin- and cubilin-mediated endocytosis of albumin in proximal-tubule-derived opossum kidney cells. J. Physiol. 552471–81 [Google Scholar]
  107. Slattery C, Jenkin KA, Lee A, Simcocks AC, McAinch AJ. 107.  et al. 2011. Na+-H+ exchanger regulatory factor 1 (NHERF1) PDZ scaffold binds an internal binding site in the scavenger receptor megalin. Cell. Physiol. Biochem. 27:171–78 [Google Scholar]
  108. Hryciw DH, Jenkin KA, Simcocks AC, Grinfeld E, McAinch AJ, Poronnik P. 108.  2012. The interaction between megalin and ClC-5 is scaffolded by the Na+-H+ exchanger regulatory factor 2 (NHERF2) in proximal tubule cells. Int. J. Biochem. Cell Biol. 44815–23 [Google Scholar]
  109. Biemesderfer D, Nagy T, DeGray B, Aronson PS. 109.  1999. Specific association of megalin and the Na+/H+ exchanger isoform NHE3 in the proximal tubule. J. Biol. Chem. 274:17518–24 [Google Scholar]
  110. Lee A, Slattery C, Nikolic-Paterson DJ, Hryciw DH, Wilk S. 110.  et al. 2015. Chloride channel ClC-5 binds to aspartyl aminopeptidase to regulate renal albumin endocytosis. Am. J. Physiol. Renal Physiol. 308F784–92 [Google Scholar]
  111. Hryciw DH, Ekberg J, Lee A, Lensink IL, Kumar S. 111.  et al. 2004. Nedd4-2 functionally interacts with ClC-5: involvement in constitutive albumin endocytosis in proximal tubule cells. J. Biol. Chem. 279:54996–5007 [Google Scholar]
  112. Dobrinskikh E, Lewis L, Brian Doctor R, Okamura K, Lee MG. 112.  et al. 2015. Shank2 regulates renal albumin endocytosis. Physiol. Rep. 3e12510 [Google Scholar]
  113. Ferrell N, Ricci KB, Groszek J, Marmerstein JT, Fissell WH. 113.  2012. Albumin handling by renal tubular epithelial cells in a microfluidic bioreactor. Biotechnol. Bioeng. 109:797–803 [Google Scholar]
  114. Schnatwinkel C, Christoforidis S, Lindsay MR, Uttenweiler-Joseph S, Wilm M. 114.  et al. 2004. The Rab5 effector Rabankyrin-5 regulates and coordinates different endocytic mechanisms. PLOS Biol. 2E261 [Google Scholar]
  115. Pohl M, Shan Q, Petsch T, Styp-Rekowska B, Matthey P. 115.  et al. 2015. Short-term functional adaptation of aquaporin-1 surface expression in the proximal tubule, a component of glomerulotubular balance. J. Am. Soc. Nephrol. 26:1269–78 [Google Scholar]
  116. Kolb RJ, Woost PG, Hopfer U. 116.  2004. Membrane trafficking of angiotensin receptor type-1 and mechanochemical signal transduction in proximal tubule cells. Hypertension 44352–59 [Google Scholar]
  117. Duan Y, Weinstein AM, Weinbaum S, Wang T. 117.  2010. Shear stress-induced changes of membrane transporter localization and expression in mouse proximal tubule cells. PNAS 107:21860–65 [Google Scholar]
  118. Nielsen R, Christensen EI, Birn H. 118.  2016. Megalin and cubilin in proximal tubule protein reabsorption: from experimental models to human disease. Kidney Int. 8958–67 [Google Scholar]
  119. Wilmer MJ, Emma F, Levtchenko EN. 119.  2010. The pathogenesis of cystinosis: mechanisms beyond cystine accumulation. Am. J. Physiol. Renal Physiol. 299:F905–16 [Google Scholar]
  120. Sansanwal P, Yen B, Gahl WA, Ma Y, Ying L. 120.  et al. 2010. Mitochondrial autophagy promotes cellular injury in nephropathic cystinosis. J. Am. Soc. Nephrol. 21:272–83 [Google Scholar]
  121. Napolitano G, Johnson JL, He J, Rocca CJ, Monfregola J. 121.  et al. 2015. Impairment of chaperone-mediated autophagy leads to selective lysosomal degradation defects in the lysosomal storage disease cystinosis. EMBO Mol. Med. 7158–74 [Google Scholar]
  122. Gaide Chevronnay HP, Janssens V, Van Der Smissen P, N'Kuli F, Nevo N. 122.  et al. 2014. Time course of pathogenic and adaptation mechanisms in cystinotic mouse kidneys. J. Am. Soc. Nephrol. 25:1256–69 [Google Scholar]
  123. Wilmer MJ, Christensen EI, van den Heuvel LP, Monnens LA, Levtchenko EN. 123.  2008. Urinary protein excretion pattern and renal expression of megalin and cubilin in nephropathic cystinosis. Am. J. Kidney Dis. 51893–903 [Google Scholar]
  124. Johnson JL, Napolitano G, Monfregola J, Rocca CJ, Cherqui S, Catz SD. 124.  2013. Upregulation of the Rab27a-dependent trafficking and secretory mechanisms improves lysosomal transport, alleviates endoplasmic reticulum stress, and reduces lysosome overload in cystinosis. Mol. Cell. Biol. 332950–62 [Google Scholar]
  125. Devuyst O, Thakker RV. 125.  2010. Dent's disease. Orphanet J. Rare Dis. 528 [Google Scholar]
  126. Günther W, Lüchow A, Cluzeaud F, Vandewalle A, Jentsch TJ. 126.  1998. ClC-5, the chloride channel mutated in Dent's disease, colocalizes with the proton pump in endocytotically active kidney cells. PNAS 958075–80 [Google Scholar]
  127. Piwon N, Günther W, Schwake M, Bösl MR, Jentsch TJ. 127.  2000. ClC-5 Cl−-channel disruption impairs endocytosis in a mouse model for Dent's disease. Nature 408369–73 [Google Scholar]
  128. Maritzen T, Lisi S, Botta R, Pinchera A, Fanelli G. 128.  et al. 2006. ClC-5 does not affect megalin expression and function in the thyroid. Thyroid 16:725–30 [Google Scholar]
  129. Gorvin CM, Wilmer MJ, Piret SE, Harding B, van den Heuvel LP. 129.  et al. 2013. Receptor-mediated endocytosis and endosomal acidification is impaired in proximal tubule epithelial cells of Dent disease patients. PNAS 110:7014–19 [Google Scholar]
  130. Novarino G, Weinert S, Rickheit G, Jentsch TJ. 130.  2010. Endosomal chloride-proton exchange rather than chloride conductance is crucial for renal endocytosis. Science 328:1398–401 [Google Scholar]
  131. Rickheit G, Wartosch L, Schaffer S, Stobrawa SM, Novarino G. 131.  et al. 2010. Role of ClC-5 in renal endocytosis is unique among ClC exchangers and does not require PY-motif-dependent ubiquitylation. J. Biol. Chem. 285:17595–603 [Google Scholar]
  132. Schwake M, Friedrich T, Jentsch TJ. 132.  2001. An internalization signal in ClC-5, an endosomal Cl− channel mutated in Dent's disease. J. Biol. Chem. 276:12049–54 [Google Scholar]
  133. Bokenkamp A, Ludwig M. 133.  2016. The oculocerebrorenal syndrome of Lowe: an update. Pediatr. Nephrol. In press. doi:10.1007/s00467-016-3343-3 [Google Scholar]
  134. Dressman MA, Olivos-Glander IM, Nussbaum RL, Suchy SF. 134.  2000. Ocrl1, a PtdIns(4,5)P(2) 5-phosphatase, is localized to the trans-Golgi network of fibroblasts and epithelial cells. J. Histochem. Cytochem. 48179–90 [Google Scholar]
  135. Mehta ZB, Pietka G, Lowe M. 135.  2014. The cellular and physiological functions of the Lowe syndrome protein OCRL1. Traffic 15:471–87 [Google Scholar]
  136. Janne PA, Suchy SF, Bernard D, MacDonald M, Crawley J. 136.  et al. 1998. Functional overlap between murine Inpp5b and Ocrl1 may explain why deficiency of the murine ortholog for OCRL1 does not cause Lowe syndrome in mice. J. Clin. Investig. 101:2042–53 [Google Scholar]
  137. Bothwell SP, Chan E, Bernardini IM, Kuo YM, Gahl WA, Nussbaum RL. 137.  2011. Mouse model for Lowe syndrome/Dent Disease 2 renal tubulopathy. J. Am. Soc. Nephrol. 22:443–48 [Google Scholar]
  138. Zhang X, Jefferson AB, Auethavekiat V, Majerus PW. 138.  1995. The protein deficient in Lowe syndrome is a phosphatidylinositol-4,5-bisphosphate 5-phosphatase. PNAS 924853–56 [Google Scholar]
  139. Guerriero CJ, Weixel KM, Bruns JR, Weisz OA. 139.  2006. Phosphatidylinositol 5-kinase stimulates apical biosynthetic delivery via an Arp2/3-dependent mechanism. J. Biol. Chem. 281:15376–84 [Google Scholar]
  140. Allen PG. 140.  2003. Actin filament uncapping localizes to ruffling lamellae and rocketing vesicles. Nat. Cell Biol. 5972–79 [Google Scholar]
  141. Ungewickell AJ, Majerus PW. 141.  1999. Increased levels of plasma lysosomal enzymes in patients with Lowe syndrome. PNAS 9613342–44 [Google Scholar]
  142. Choudhury R, Diao A, Zhang F, Eisenberg E, Saint-Pol A. 142.  et al. 2005. Lowe syndrome protein OCRL1 interacts with clathrin and regulates protein trafficking between endosomes and the trans-Golgi network. Mol. Biol. Cell 16:3467–79 [Google Scholar]
  143. Cui S, Guerriero CJ, Szalinski CM, Kinlough CL, Hughey RP, Weisz OA. 143.  2010. OCRL1 function in renal epithelial membrane traffic. Am. J. Physiol. Renal Physiol. 298:F335–45 [Google Scholar]
  144. Nielsen R, Courtoy PJ, Jacobsen C, Dom G, Lima WR. 144.  et al. 2007. Endocytosis provides a major alternative pathway for lysosomal biogenesis in kidney proximal tubular cells. PNAS 104:5407–12 [Google Scholar]
  145. Nandez R, Balkin DM, Messa M, Liang L, Paradise S. 145.  et al. 2014. A role of OCRL in clathrin-coated pit dynamics and uncoating revealed by studies of Lowe syndrome cells. eLife 3e02975 [Google Scholar]
  146. Noakes CJ, Lee G, Lowe M. 146.  2011. The PH domain proteins IPIP27A and B link OCRL1 to receptor recycling in the endocytic pathway. Mol. Biol. Cell 22:606–23 [Google Scholar]
  147. Vicinanza M, Di Campli A, Polishchuk E, Santoro M, Di Tullio G. 147.  et al. 2011. OCRL controls trafficking through early endosomes via PtdIns4,5P(2)-dependent regulation of endosomal actin. EMBO J. 304970–85 [Google Scholar]
  148. Oltrabella F, Pietka G, Ramirez IB, Mironov A, Starborg T. 148.  et al. 2015. The Lowe syndrome protein OCRL1 is required for endocytosis in the zebrafish pronephric tubule. PLOS Genet. 11e1005058 [Google Scholar]
  149. Dambournet D, Machicoane M, Chesneau L, Sachse M, Rocancourt M. 149.  et al. 2011. Rab35 GTPase and OCRL phosphatase remodel lipids and F-actin for successful cytokinesis. Nat. Cell Biol. 13:981–88 [Google Scholar]
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Receptor-Mediated Endocytosis in the Proximal Tubule
Annual Review of Physiology 79, 425 (2017); https://doi.org/10.1146/annurev-physiol-022516-034234
/content/journals/10.1146/annurev-physiol-022516-034234
/content/journals/10.1146/annurev-physiol-022516-034234
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