Nuclear translocation of IQGAP1 protein upon exposure to puromycin aminonucleoside in cultured human podocytes: ERK pathway involvement

Claire C Rigothier*, Moin Ahson Saleem, Chantal Bourget, Peter W Mathieson, Christian Combe, Gavin Iain Welsh

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

5 Citations (Scopus)
233 Downloads (Pure)

Abstract

IQGAP1, a protein that links the actin cytoskeleton to slit diaphragm proteins, is involved in podocyte motility and permeability. Its regulation in glomerular disease is not known. We have exposed human podocytes to puromycin aminonucleoside (PAN), an inducer of nephrotic syndrome in rats, and studied the effects on IQGAP1 biology and function. In human podocytes exposed to PAN, a nuclear translocation of IQGAP1 was observed by immunocytolocalization and confirmed by Western blot after selective nuclear/cytoplasmic extraction. In contrast to IQGAP1, IQGAP2 expression remained cytoplasmic. IQGAP1 nuclear translocation was associated with a significant decrease in its interaction with nephrin and podocalyxin. Activation of the ERK pathway was observed in PAN treated podocytes with a preponderant nuclear localization of the phosphorylated form of ERK (P-ERK). The interaction between IQGAP1 and P-ERK increased upon podocyte exposure to PAN. Inhibitors of ERK pathway activation blocked IQGAP1 nuclear translocation (p<0.02). Chromatin interaction protein assays demonstrated an interaction of IQGAP1 with chromatin and with Histone H3, which increased in response to PAN. In summary, PAN induces the ERK dependent translocation of IQGAP1 into the nuclei in human podocytes which leads to the interaction of IQGAP1 with chromatin and Histone H3, and decreased interactions between IQGAP1 and slit-diaphragm proteins. Therefore, IQGAP1 may have a role in podocyte gene regulation in glomerular disease.
Original languageEnglish
Pages (from-to)1470-1478
Number of pages9
JournalCellular Signalling
Volume28
Issue number10
Early online date1 Jul 2016
DOIs
Publication statusPublished - 1 Oct 2016

Keywords

  • IQGAP1
  • MAP kinase pathway
  • Nucleus
  • Podocytes
  • Slit diaphragm proteins

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