Advertisement

Site-specific expression of IQGAP1 in human nephrons

  • Ping Wang
  • Xiaojie Gong
  • Peizhong Guan
  • Dong Ji
  • Linna Du
  • Dongmei Xu
  • Yipeng LiuEmail author
Original Paper

Abstract

IQGAP1 is a multifunctional, 190-kDa scaffolding protein that plays an important role in the regulation of cell adhesion, migration, proliferation, differentiation, polarization and cytoskeletal remodeling. IQGAP1 is ubiquitously expressed in human organs and is highly expressed in the kidney. Currently, the site-specific expression of IQGAP1 in the human nephrons is unclear. We performed Western blotting analysis, immunohistochemistry and double-immunolabeling confocal microscopic analysis of IQGAP1 with specific biomarkers of each nephron segment to study the expression and distribution of IQGAP1 in human nephrons. We found that IQGAP1 was strongly expressed in human podocytes and glomerular endothelial cells, but weakly expressed in glomerular mesangial cells. In human renal tubules, IQGAP1 was strongly expressed in the collecting duct, moderately expressed in the proximal tubule, medullary loop, distal convoluted tubule and connecting tubule. IQGAP1 staining was much stronger in the apical membrane in the proximal tubule, thick descending limb and thick ascending limb of medullary loop and collecting duct. However, the expression of IQGAP1 was mainly in the basolateral membrane of the connecting tubule, and diffusely in the thin limb of medullary loop and distal convoluted tubule. The interaction between IQGAP1 and F-actin suggested that cytoskeleton regulation may be the underlying mechanism mediating the effect of IQGAP1 in human nephrons. To the best of our knowledge, this is the first report of specific expression and differential subcellular location of IQGAP1 in human nephrons. The site-specific expression pattern of IQGAP1 suggests that IQGAP1 may play diverse roles in various human nephron segments.

Keywords

IQGAP1 Human glomeruli Human renal tubules F-actin 

Notes

Acknowledgements

This study was supported by grants from the National Natural Science Foundation of China (Grant No. 81500555), the Third Project of Jinan City Science and Technology Development Plan (Grant No. 201503002), Young Taishan Scholars Program and the Medicine and Health Science Technology Development Projects of Shandong Province (Grant No. 2016WS0501).

Compliance with ethical standards

Conflict of interest

All the authors declare that there are no competing interests.

References

  1. Bhattacharya M et al (2014) IQGAP1-dependent scaffold suppresses RhoA and inhibits airway smooth muscle contraction. J Clin Invest 124:4895–4898.  https://doi.org/10.1172/JCI76658 CrossRefGoogle Scholar
  2. Cheung KL, Lee JH, Shu L, Kim JH, Sacks DB, Kong AN (2013) The Ras GTPase-activating-like protein IQGAP1 mediates Nrf2 protein activation via the mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK)-ERK pathway. J Biol Chem 288:22378–22386.  https://doi.org/10.1074/jbc.M112.444182 CrossRefGoogle Scholar
  3. Fram S, King H, Sacks DB, Wells CM (2014) A PAK6-IQGAP1 complex promotes disassembly of cell-cell adhesions. Cell Mol Life Sci 71:2759–2773.  https://doi.org/10.1007/s00018-013-1528-5 CrossRefGoogle Scholar
  4. Fukata M, Nakagawa M, Itoh N, Kawajiri A, Yamaga M, Kuroda S, Kaibuchi K (2001) Involvement of IQGAP1, an effector of Rac1 and Cdc42 GTPases, in cell-cell dissociation during cell scattering. Mol Cell Biol 21:2165–2183.  https://doi.org/10.1128/MCB.21.6.2165-2183.2001 CrossRefGoogle Scholar
  5. Grahammer F, Schell C, Huber TB (2013) The podocyte slit diaphragm–from a thin grey line to a complex signalling hub. Nat Rev Nephrol 9:587–598.  https://doi.org/10.1038/nrneph.2013.169 CrossRefGoogle Scholar
  6. Ikeda M, Matsuzaki T (2015) Regulation of aquaporins by vasopressin in the kidney. Vitam Horm 98:307–337.  https://doi.org/10.1016/bs.vh.2014.12.008 CrossRefGoogle Scholar
  7. Jausoro I, Mestres I, Quassollo G, Masseroni L, Heredia F, Caceres A (2013) Regulation of spine density and morphology by IQGAP1 protein domains. PLoS ONE 8:e56574.  https://doi.org/10.1371/journal.pone.0056574 CrossRefGoogle Scholar
  8. Jung HJ, Kwon TH (2016) Molecular mechanisms regulating aquaporin-2 in kidney collecting duct. Am J Physiol Renal Physiol 311:F1318–F1328.  https://doi.org/10.1152/ajprenal.00485.2016 CrossRefGoogle Scholar
  9. Kimura T et al (2013) Activated Cdc42-bound IQGAP1 determines the cellular endocytic site. Mol Cell Biol 33:4834–4843.  https://doi.org/10.1128/MCB.00895-13 CrossRefGoogle Scholar
  10. Lai LW, Yong KC, Lien YH (2008) Site-specific expression of IQGAP1, a key mediator of cytoskeleton, in mouse renal tubules. J Histochem Cytochem 56:659–666.  https://doi.org/10.1369/jhc.2008.950113 CrossRefGoogle Scholar
  11. Li CH et al (2018) Overexpression of IQGAP1 promotes the angiogenesis of esophageal squamous cell carcinoma through the AKT and ERKmediated VEGFVEGFR2 signaling pathway. Oncol Rep 40:1795–1802.  https://doi.org/10.3892/or.2018.6558 Google Scholar
  12. Liu Y et al (2013) IQGAP1 mediates angiotensin II-induced apoptosis of podocytes via the ERK1/2 MAPK signaling pathway. Am J Nephrol 38:430–444.  https://doi.org/10.1159/000355970 CrossRefGoogle Scholar
  13. Liu Y et al (2015) IQGAP1 regulates actin cytoskeleton organization in podocytes through interaction with nephrin. Cell Signal 27:867–877.  https://doi.org/10.1016/j.cellsig.2015.01.015 CrossRefGoogle Scholar
  14. Logue JS, Whiting JL, Tunquist B, Sacks DB, Langeberg LK, Wordeman L, Scott JD (2011) AKAP220 protein organizes signaling elements that impact cell migration. J Biol Chem 286:39269–39281.  https://doi.org/10.1074/jbc.M111.277756 CrossRefGoogle Scholar
  15. Magill DJ, Hamilton E, Shirran SL, Botting CH, Timson DJ (2016) On the interaction between human IQGAP1 and actin protein. Pept Lett 23:386–395CrossRefGoogle Scholar
  16. Mobasheri A, Wray S, Marples D (2005) Distribution of AQP2 and AQP3 water channels in human tissue microarrays. J Mol Histol 36:1–14.  https://doi.org/10.1007/s10735-004-2633-4 CrossRefGoogle Scholar
  17. Nedvetsky PI, Tamma G, Beulshausen S, Valenti G, Rosenthal W, Klussmann E (2009) Regulation of aquaporin-2 trafficking. In: Beitz E (ed) Aquaporins. Handbook of experimental pharmacology. Springer, Berlin, pp 133–157.  https://doi.org/10.1007/978-3-540-79885-9_6 Google Scholar
  18. Nouri K et al (2016) IQGAP1 Interaction with RHO family proteins revisited: kinetic and equilibrium evidence for multiple distinct binding sites. J Biol Chem 291:26364–26376.  https://doi.org/10.1074/jbc.M116.752121 CrossRefGoogle Scholar
  19. Okutsu R, Rai T, Kikuchi A, Ohno M, Uchida K, Sasaki S, Uchida S (2008) AKAP220 colocalizes with AQP2 in the inner medullary collecting ducts. Kidney Int 74:1429–1433.  https://doi.org/10.1038/ki.2008.402 CrossRefGoogle Scholar
  20. Pelikan-Conchaudron A, Le Clainche C, Didry D, Carlier MF (2011) The IQGAP1 protein is a calmodulin-regulated barbed end capper of actin filaments: possible implications in its function in cell migration. J Biol Chem 286:35119–35128.  https://doi.org/10.1074/jbc.M111.258772 CrossRefGoogle Scholar
  21. Rigothier C et al (2012) IQGAP1 interacts with components of the slit diaphragm complex in podocytes and is involved in podocyte migration and permeability in vitro. PLoS ONE 7:e37695.  https://doi.org/10.1371/journal.pone.0037695 CrossRefGoogle Scholar
  22. Robert B, Zhao X, Abrahamson DR (2000) Coexpression of neuropilin-1, Flk1, and VEGF(164) in developing and mature mouse kidney glomeruli. Am J Physiol Renal Physiol 279:F275–F282.  https://doi.org/10.1152/ajprenal.2000.279.2.F275 CrossRefGoogle Scholar
  23. Sbroggio M et al (2011) IQGAP1 regulates ERK1/2 and AKT signalling in the heart and sustains functional remodelling upon pressure overload. Cardiovasc Res 91:456–464.  https://doi.org/10.1093/cvr/cvr103 CrossRefGoogle Scholar
  24. Suyama M et al (2018) Forced expression of vascular endothelial growth factor-A in podocytes decreases mesangial cell numbers and attenuates endothelial cell differentiation in the mouse glomerulus. Clin Exp Nephrol 22:266–274.  https://doi.org/10.1007/s10157-017-1450-5 CrossRefGoogle Scholar
  25. Swiech L et al (2011) CLIP-170 and IQGAP1 cooperatively regulate dendrite morphology. J Neurosci 31:4555–4568.  https://doi.org/10.1523/JNEUROSCI.6582-10.2011 CrossRefGoogle Scholar
  26. Szaszi K, Amoozadeh Y (2014) New insights into functions, regulation, and pathological roles of tight junctions in kidney tubular epithelium. Int Rev Cell Mol Biol 308:205–271.  https://doi.org/10.1016/B978-0-12-800097-7.00006-3 CrossRefGoogle Scholar
  27. Wang X et al (2014) Histone deacetylase 4 selectively contributes to podocyte injury in diabetic nephropathy. Kidney Int 86:712–725.  https://doi.org/10.1038/ki.2014.111 CrossRefGoogle Scholar
  28. Watanabe T et al (2004) Interaction with IQGAP1 links APC to Rac1, Cdc42, and actin filaments during cell polarization and. migration. Dev Cell 7:871–883.  https://doi.org/10.1016/j.devcel.2004.10.017 CrossRefGoogle Scholar
  29. Weissbach L, Settleman J, Kalady MF, Snijders AJ, Murthy AE, Yan YX, Bernards A (1994) Identification of a human rasGAP-related protein containing calmodulin-binding motifs. J Biol Chem 269:20517–20521Google Scholar
  30. Whiting JL et al (2016) AKAP220 manages apical actin networks that coordinate aquaporin-2 location and renal water reabsorption. Proc Natl Acad Sci USA 113:E4328–E4337.  https://doi.org/10.1073/pnas.1607745113 CrossRefGoogle Scholar
  31. Yamaoka-Tojo M et al (2004) IQGAP1, a novel vascular endothelial growth factor receptor binding protein, is involved in reactive oxygen species–dependent endothelial migration and proliferation. Circ Res 95:276–283.  https://doi.org/10.1161/01.RES.0000136522.58649.60 CrossRefGoogle Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Ping Wang
    • 1
  • Xiaojie Gong
    • 1
  • Peizhong Guan
    • 2
  • Dong Ji
    • 3
  • Linna Du
    • 1
  • Dongmei Xu
    • 1
  • Yipeng Liu
    • 1
    Email author
  1. 1.Department of Nephrology, Shandong Provincial Qianfoshan HospitalShandong UniversityJinanChina
  2. 2.Department of NephrologyYEDA HospitalYantaiChina
  3. 3.Department of DialysisHuimin County People’s HospitalBinzhouChina

Personalised recommendations