Display options
Cite
Lennon R, Randles MJ, Humphries MJ. The importance of podocyte adhesion for a healthy glomerulus. Front Endocrinol (Lausanne). 2014;5:160doi: 10.3389/fendo.2014.00160.
Lennon, R., Randles, M. J., & Humphries, M. J. (2014). The importance of podocyte adhesion for a healthy glomerulus. Frontiers in endocrinology, 5160. https://doi.org/10.3389/fendo.2014.00160
Lennon, Rachel, et al. "The importance of podocyte adhesion for a healthy glomerulus." Frontiers in endocrinology vol. 5 (2014): 160. doi: https://doi.org/10.3389/fendo.2014.00160
Lennon R, Randles MJ, Humphries MJ. The importance of podocyte adhesion for a healthy glomerulus. Front Endocrinol (Lausanne). 2014 Oct 14;5:160. doi: 10.3389/fendo.2014.00160. eCollection 2014. PMID: 25352829; PMCID: PMC4196579.
Copy Download .nbib Format: NLM
Share it on

Front Endocrinol (Lausanne). 2014 Oct 14;5:160. doi: 10.3389/fendo.2014.00160. eCollection 2014.

The importance of podocyte adhesion for a healthy glomerulus.

Frontiers in endocrinology

Rachel Lennon, Michael J Randles, Martin J Humphries

Affiliations

  1. Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, The University of Manchester , Manchester , UK ; Institute of Human Development, Faculty of Medical and Human Sciences, The University of Manchester , Manchester , UK ; Department of Paediatric Nephrology, Manchester Academic Health Science Centre, Central Manchester University Hospitals NHS Foundation Trust , Manchester , UK.
  2. Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, The University of Manchester , Manchester , UK ; Institute of Human Development, Faculty of Medical and Human Sciences, The University of Manchester , Manchester , UK.
  3. Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, The University of Manchester , Manchester , UK.

PMID: 25352829 PMCID: PMC4196579 DOI: 10.3389/fendo.2014.00160

Abstract

Podocytes are specialized epithelial cells that cover the outer surfaces of glomerular capillaries. Unique cell junctions, known as slit diaphragms, which feature nephrin and Neph family proteins in addition to components of adherens, tight, and gap junctions, connect adjacent podocyte foot processes. Single gene disorders affecting the slit diaphragm result in nephrotic syndrome in humans, characterized by massive loss of protein across the capillary wall. In addition to specialized cell junctions, interconnecting podocytes also adhere to the glomerular basement membrane (GBM) of the capillary wall. The GBM is a dense network of secreted, extracellular matrix (ECM) components and contains tissue-restricted isoforms of collagen IV and laminin in addition to other structural proteins and ECM regulators such as proteases and growth factors. The specialized niche of the GBM provides a scaffold for endothelial cells and podocytes to support their unique functions and human genetic mutations in GBM components lead to renal failure, thus highlighting the importance of cell-matrix interactions in the glomerulus. Cells adhere to ECM via adhesion receptors, including integrins, syndecans, and dystroglycan and in particular the integrin heterodimer α3β1 is required to maintain barrier integrity. Therefore, the sophisticated function of glomerular filtration relies on podocyte adhesion both at cell junctions and at the interface with the ECM. In health, the podocyte coordinates signals from cell junctions and cell-matrix interactions, in response to environmental cues in order to regulate filtration and as our understanding of mechanisms that control cell adhesion in the glomerulus develops, then insight into the effects of disease will improve. The ultimate goal will be to develop targeted therapies to prevent or repair defects in the filtration barrier and to restore glomerular function.

Keywords: adhesion and signaling molecules; cell junction; extracellular matrix; nephrotic syndrome; podocyte

References

  1. Nat Cell Biol. 2011 Apr;13(4):383-93 - PubMed
  2. J Histochem Cytochem. 1998 Apr;46(4):449-57 - PubMed
  3. PLoS One. 2014 Jun 10;9(6):e99083 - PubMed
  4. Proc Natl Acad Sci U S A. 2005 Jul 12;102(28):9814-9 - PubMed
  5. Dev Cell. 2013 Mar 11;24(5):472-85 - PubMed
  6. PLoS One. 2012;7(11):e50996 - PubMed
  7. J Biol Chem. 2001 Apr 6;276(14):10906-12 - PubMed
  8. J Cell Biol. 1993 Aug;122(4):809-23 - PubMed
  9. J Neurogenet. 2014 Sep-Dec;28(3-4):270-81 - PubMed
  10. J Cell Biol. 2001 Apr 30;153(3):585-98 - PubMed
  11. Dev Biol. 2008 Apr 15;316(2):288-301 - PubMed
  12. J Am Soc Nephrol. 2014 May;25(5):953-66 - PubMed
  13. Cell. 2012 Oct 12;151(2):384-99 - PubMed
  14. J Cell Biol. 1999 Nov 29;147(5):1109-22 - PubMed
  15. Nature. 2009 Jan 15;457(7227):322-6 - PubMed
  16. Dev Biol. 2008 Jan 15;313(2):584-93 - PubMed
  17. J Struct Biol. 1996 Mar-Apr;116(2):270-7 - PubMed
  18. Cell. 2003 Apr 4;113(1):37-47 - PubMed
  19. Am J Pathol. 2000 May;156(5):1749-65 - PubMed
  20. Nat Genet. 2000 Apr;24(4):349-54 - PubMed
  21. Blood. 2004 Oct 15;104(8):2217-23 - PubMed
  22. Sci Signal. 2009 Sep 08;2(87):ra51 - PubMed
  23. J Biol Chem. 1995 Apr 21;270(16):9398-406 - PubMed
  24. Kidney Int. 2003 Feb;63(2):438-46 - PubMed
  25. Mol Biol Cell. 1998 Jul;9(7):1803-16 - PubMed
  26. Cell Adhes Commun. 1998 Mar;5(3):177-92 - PubMed
  27. Cell. 2014 Jan 30;156(3):482-94 - PubMed
  28. Development. 2004 May;131(10):2247-56 - PubMed
  29. Mol Cell Biol. 2001 Jul;21(14):4829-36 - PubMed
  30. J Cell Sci. 2006 Jun 15;119(Pt 12):2445-56 - PubMed
  31. J Clin Invest. 2012 Jan;122(1):348-58 - PubMed
  32. J Cell Biol. 1999 Jan 11;144(1):151-60 - PubMed
  33. Kidney Int. 2007 Nov;72(10):1181-3 - PubMed
  34. J Cell Sci. 2009 Jan 15;122(Pt 2):165-70 - PubMed
  35. J Am Soc Nephrol. 2004 Aug;15(8):2079-89 - PubMed
  36. J Am Soc Nephrol. 2000 Jun;11(6):991-1001 - PubMed
  37. J Exp Med. 1961 Jan 1;113:47-66 - PubMed
  38. Matrix Biol. 2006 Sep;25(7):443-56 - PubMed
  39. J Comp Pathol. 1997 Oct;117(3):209-25 - PubMed
  40. N Engl J Med. 2012 Apr 19;366(16):1508-14 - PubMed
  41. J Clin Invest. 2012 Dec;122(12):4375-87 - PubMed
  42. J Am Soc Nephrol. 2014 Apr;25(4):687-92 - PubMed
  43. Nat Genet. 2000 Mar;24(3):251-6 - PubMed
  44. Nat Genet. 1995 Jun;10(2):229-34 - PubMed
  45. J Cell Biol. 2001 Mar 5;152(5):1007-18 - PubMed
  46. Nat Genet. 2005 Jul;37(7):739-44 - PubMed
  47. Proc Natl Acad Sci U S A. 2011 Sep 13;108(37):15348-53 - PubMed
  48. Physiol Rev. 2004 Oct;84(4):1315-39 - PubMed
  49. J Biol Chem. 1988 Apr 15;263(11):5425-30 - PubMed
  50. Nat Rev Nephrol. 2011 Nov 01;8(1):52-6 - PubMed
  51. Cell Rep. 2012 Jul 26;2(1):52-61 - PubMed
  52. FASEB J. 2001 Aug;15(10):1843-5 - PubMed
  53. J Renin Angiotensin Aldosterone Syst. 2010 Sep;11(3):149-57 - PubMed
  54. EMBO J. 2010 Jan 20;29(2):281-91 - PubMed
  55. FEBS Lett. 2007 Feb 20;581(4):644-50 - PubMed
  56. J Am Soc Nephrol. 2008 Oct;19(10):1871-8 - PubMed
  57. Mol Cell. 1998 Mar;1(4):575-82 - PubMed
  58. J Biol Chem. 2013 Mar 22;288(12):8238-49 - PubMed
  59. J Clin Invest. 2012 Dec;122(12 ):4401-11 - PubMed
  60. J Am Soc Nephrol. 2010 Jul;21(7):1145-56 - PubMed
  61. J Cell Biol. 2007 Dec 3;179(5):1043-57 - PubMed
  62. J Am Soc Nephrol. 2007 Nov;18(11):2885-93 - PubMed
  63. Lab Invest. 1978 Aug;39(2):90-100 - PubMed
  64. J Am Soc Nephrol. 2000 Jan;11(1):1-8 - PubMed
  65. J Mol Biol. 1993 Jan 5;229(1):146-52 - PubMed
  66. Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):5192-6 - PubMed
  67. Matrix Biol. 2006 Apr;25(3):189-97 - PubMed
  68. J Biochem. 2014 Aug;156(2):115-28 - PubMed
  69. Kidney Int. 2011 Feb;79(3):311-6 - PubMed
  70. J Cell Biol. 2006 Oct 9;175(1):33-9 - PubMed
  71. J Cell Sci. 2005 Jul 1;118(Pt 13):2913-21 - PubMed
  72. Proteomics. 2012 Jul;12(13):2107-14 - PubMed
  73. Cell Metab. 2010 Oct 6;12(4):329-40 - PubMed
  74. Nat Genet. 1995 Aug;10(4):400-6 - PubMed
  75. Mol Cell Biol. 2005 Aug;25(15):6846-56 - PubMed
  76. N Engl J Med. 2003 Jun 19;348(25):2543-56 - PubMed
  77. Am J Physiol Renal Physiol. 2011 Mar;300(3):F811-20 - PubMed
  78. Nature. 2006 Apr 6;440(7085):818-23 - PubMed
  79. Hum Mutat. 2010 Sep;31(9):992-1002 - PubMed
  80. Nat Med. 2013 Oct;19(10):1288-96 - PubMed
  81. J Biol Chem. 1993 Aug 15;268(23):17286-99 - PubMed
  82. Nature. 2009 Oct 15;461(7266):1002-6 - PubMed
  83. J Cell Biol. 1974 Dec;63(3):883-903 - PubMed
  84. Nat Rev Nephrol. 2013 Oct;9(10):587-98 - PubMed
  85. Nature. 1996 Jan 4;379(6560):91-6 - PubMed
  86. J Clin Invest. 2014 Mar;124(3):1098-113 - PubMed
  87. J Neurogenet. 2014 Sep-Dec;28(3-4):264-9 - PubMed
  88. J Am Soc Nephrol. 2013 May;24(6):917-29 - PubMed
  89. Nat Med. 2008 Dec;14(12):1370-6 - PubMed
  90. Am J Pathol. 2001 Nov;159(5):1735-42 - PubMed
  91. J Biol Chem. 2003 Jun 6;278(23):20716-23 - PubMed
  92. J Cell Sci. 2006 Oct 1;119(Pt 19):3901-3 - PubMed
  93. Am J Kidney Dis. 2000 Jul;36(1):190-6 - PubMed
  94. J Am Soc Nephrol. 2006 Aug;17(8):2164-75 - PubMed
  95. Nat Rev Mol Cell Biol. 2009 Dec;10(12):843-53 - PubMed
  96. Kidney Int. 2008 Aug;74(3):289-99 - PubMed
  97. J Cell Biol. 1994 Nov;127(3):879-91 - PubMed
  98. J Cell Biol. 1997 May 5;137(3):685-701 - PubMed
  99. Nat Genet. 1999 Nov;23(3):354-8 - PubMed
  100. Mol Cell Biol. 2013 Dec;33(23):4755-64 - PubMed
  101. Proc Natl Acad Sci U S A. 1999 Jul 6;96(14):7962-7 - PubMed
  102. Nat Med. 2011 Jul 31;17(8):952-60 - PubMed
  103. J Biol Chem. 2012 Dec 28;287(53):44270-7 - PubMed
  104. Kidney Int. 2008 Mar;73(5):556-66 - PubMed
  105. Curr Opin Nephrol Hypertens. 2014 Jul;23(4):420-30 - PubMed
  106. Am J Pathol. 2003 Dec;163(6):2337-46 - PubMed
  107. J Am Soc Nephrol. 2014 May;25(5):939-51 - PubMed
  108. J Cell Biol. 2011 Oct 31;195(3):499-513 - PubMed
  109. Cell. 2002 Sep 20;110(6):673-87 - PubMed
  110. Oncogene. 2011 Oct 27;30(43):4375-85 - PubMed
  111. Elife. 2013 Oct 08;2:e01149 - PubMed
  112. Science. 2005 Jun 17;308(5729):1801-4 - PubMed
  113. Mol Biol Cell. 2007 May;18(5):1621-33 - PubMed
  114. Curr Opin Cell Biol. 2012 Oct;24(5):607-13 - PubMed
  115. Mol Cell Biol. 2007 Dec;27(24):8698-712 - PubMed
  116. Nature. 1995 Oct 12;377(6549):539-44 - PubMed
  117. Exp Clin Transplant. 2005 Jun;3(1):283-8 - PubMed
  118. J Anat. 2007 May;210(5):578-82 - PubMed
  119. Curr Biol. 2002 May 14;12(10):787-97 - PubMed
  120. J Cell Sci. 2001 Oct;114(Pt 20):3583-90 - PubMed
  121. J Cell Sci. 2010 Apr 1;123(Pt 7):1007-13 - PubMed
  122. N Engl J Med. 2006 Mar 30;354(13):1387-401 - PubMed
  123. EMBO J. 2009 Oct 21;28(20):3132-44 - PubMed
  124. J Am Soc Nephrol. 2012 Jul;23(7):1149-54 - PubMed
  125. J Am Soc Nephrol. 2004 Jul;15(7):1731-8 - PubMed
  126. J Biol Chem. 2014 Apr 4;289(14):9502-18 - PubMed
  127. Cold Spring Harb Perspect Biol. 2011 Sep 01;3(9):a005074 - PubMed
  128. J Genet Hum. 1963 Dec;12:184-213 - PubMed
  129. J Cell Sci. 2013 Jan 15;126(Pt 2):373-8 - PubMed
  130. Kidney Int. 2012 Mar;81(5):494-501 - PubMed
  131. Kidney Int. 2013 Nov;84(5):920-30 - PubMed
  132. Cell. 2014 Jun 5;157(6):1380-92 - PubMed
  133. Genes Dev. 2003 Apr 1;17(7):926-40 - PubMed
  134. J Cell Biol. 2009 Nov 30;187(5):733-47 - PubMed
  135. J Am Soc Nephrol. 2009 Apr;20(4):798-806 - PubMed
  136. Development. 1996 Nov;122(11):3537-47 - PubMed
  137. J Cell Biol. 1996 Nov;135(4):1109-23 - PubMed
  138. Trends Cell Biol. 2006 Sep;16(9):453-60 - PubMed
  139. J Am Soc Nephrol. 2006 May;17(5):1334-44 - PubMed
  140. Nat Rev Nephrol. 2013 Apr;9(4):200-10 - PubMed
  141. Development. 2004 Apr;131(7):1619-28 - PubMed
  142. J Cell Biol. 2000 Dec 25;151(7):1435-48 - PubMed
  143. J Biol Chem. 1993 Jul 15;268(20):14972-80 - PubMed
  144. J Clin Invest. 2012 Feb;122(2):674-92 - PubMed
  145. Development. 2009 Jul;136(14):2335-44 - PubMed
  146. Mol Cell Biol. 2011 May;31(10):2134-50 - PubMed
  147. J Cell Sci. 2008 May 1;121(Pt 9):1345-7 - PubMed
  148. Biochem J. 2002 Feb 15;362(Pt 1):213-21 - PubMed
  149. J Cell Biol. 2004 Oct 11;167(1):171-81 - PubMed
  150. J Biol Chem. 1985 Jun 25;260(12):7636-44 - PubMed
  151. J Am Soc Nephrol. 2004 Oct;15(10):2514-27 - PubMed
  152. J Am Soc Nephrol. 2009 Jan;20(1):86-94 - PubMed
  153. J Cell Biol. 1990 Sep;111(3):1245-54 - PubMed
  154. J Biol Chem. 2006 Oct 27;281(43):32929-40 - PubMed
  155. Trends Pharmacol Sci. 2012 Jul;33(7):405-12 - PubMed
  156. Cell. 1996 May 17;85(4):525-35 - PubMed
  157. Am J Pathol. 2002 Nov;161(5):1597-606 - PubMed
  158. Kidney Int. 2006 Sep;70(6):1038-45 - PubMed
  159. J Am Soc Nephrol. 2010 Dec;21(12 ):2081-9 - PubMed
  160. J Biol Chem. 2000 Aug 11;275(32):24233-6 - PubMed
  161. Nephron. 1992;62(4):382-8 - PubMed
  162. N Engl J Med. 2003 Jan 9;348(2):101-8 - PubMed
  163. J Am Soc Nephrol. 2009 Jul;20(7):1491-503 - PubMed
  164. J Clin Invest. 2013 Dec;123(12):5298-309 - PubMed
  165. Mol Cell Biol. 1999 Mar;19(3):2425-34 - PubMed
  166. Mol Biol Cell. 1998 Oct;9(10):2751-65 - PubMed
  167. Lab Invest. 1976 Jan;34(1):43-59 - PubMed
  168. Kidney Int. 2010 Dec;78(11):1088-99 - PubMed
  169. Nat Rev Mol Cell Biol. 2007 Dec;8(12):957-69 - PubMed
  170. J Biol Chem. 2007 Mar 9;282(10):7457-64 - PubMed
  171. EMBO J. 1991 Nov;10(11):3137-46 - PubMed
  172. J Cell Sci. 2011 Mar 15;124(Pt 6):879-91 - PubMed
  173. Science. 2009 Sep 4;325(5945):1230-4 - PubMed
  174. EMBO Rep. 2008 Dec;9(12):1203-8 - PubMed
  175. Nat Rev Mol Cell Biol. 2014 Apr;15(4):273-88 - PubMed
  176. Nat Chem Biol. 2012 Sep;8(9):784-90 - PubMed
  177. Am J Pathol. 2008 Oct;173(4):927-37 - PubMed
  178. Nat Cell Biol. 2013 Jun;15(6):625-36 - PubMed
  179. J Clin Invest. 2006 May;116(5):1346-59 - PubMed
  180. J Am Soc Nephrol. 2013 Apr;24(5):713-21 - PubMed
  181. Nat Med. 2008 Jan;14(1):55-63 - PubMed
  182. Nephrol Dial Transplant. 2012 May;27(5):1755-68 - PubMed
  183. J Clin Invest. 2006 Aug;116(8):2272-9 - PubMed
  184. J Cell Biol. 2001 Jun 11;153(6):1251-64 - PubMed
  185. Proc Natl Acad Sci U S A. 2008 Dec 30;105(52):20677-82 - PubMed
  186. J Biol Chem. 2011 Jun 17;286(24):21886-95 - PubMed
  187. Nature. 2004 Jul 29;430(6999):583-6 - PubMed
  188. Hum Mol Genet. 2003 Dec 15;12(24):3397-405 - PubMed
  189. Science. 2009 Nov 27;326(5957):1216-9 - PubMed
  190. Curr Biol. 2013 Jun 3;23(11):1024-30 - PubMed
  191. N Engl J Med. 2013 Dec 19;369(25):2416-23 - PubMed
  192. Kidney Int. 2014 Jun;85(6):1382-94 - PubMed
  193. Science. 1999 Oct 8;286(5438):312-5 - PubMed
  194. Nephrol Dial Transplant. 2009 Jul;24(7):2044-51 - PubMed
  195. J Cell Biol. 1974 Feb;60(2):423-33 - PubMed
  196. Mol Cell Biol. 2003 Jul;23(14):4917-28 - PubMed
  197. Curr Biol. 2013 Feb 18;23(4):271-81 - PubMed
  198. Mol Cell Biol. 2003 May;23(10):3575-82 - PubMed
  199. J Cell Biol. 1990 Mar;110(3):825-32 - PubMed
  200. Dev Cell. 2006 May;10(5):625-34 - PubMed
  201. J Biol Chem. 1997 Nov 14;272(46):29330-6 - PubMed
  202. J Cell Biol. 2005 May 9;169(3):459-70 - PubMed

Publication Types

Grant support