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

hal.structure.identifierBioingénierie tissulaire [BIOTIS]
hal.structure.identifierUniversity of Bristol [Bristol]
hal.structure.identifierService de Néphrologie-transplantation-dialyse [Bordeaux]
dc.contributor.authorRIGOTHIER, Claire
hal.structure.identifierUniversity of Bristol [Bristol]
dc.contributor.authorSALEEM, Moin Ahson
hal.structure.identifierBioingénierie tissulaire [BIOTIS]
dc.contributor.authorBOURGET, Chantal
hal.structure.identifierUniversity of Bristol [Bristol]
dc.contributor.authorMATHIESON, Peter William
hal.structure.identifierService de Néphrologie-transplantation-dialyse [Bordeaux]
hal.structure.identifierBioingénierie tissulaire [BIOTIS]
dc.contributor.authorCOMBE, Christian
hal.structure.identifierUniversity of Bristol [Bristol]
dc.contributor.authorWELSH, Gavin Iain
dc.date.accessioned2021-06-10T07:03:46Z
dc.date.available2021-06-10T07:03:46Z
dc.date.issued2016-10
dc.identifier.issn0898-6568
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/78933
dc.description.abstractEnIQGAP1, 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.
dc.language.isoen
dc.publisherElsevier
dc.subject.enIQGAP1
dc.subject.enMAP kinase pathway
dc.subject.enNucleus
dc.subject.enPodocytes
dc.subject.enSlit diaphragm proteins
dc.title.enNuclear translocation of IQGAP1 protein upon exposure to puromycin aminonucleoside in cultured human podocytes: ERK pathway involvement
dc.typeArticle de revue
dc.identifier.doi10.1016/j.cellsig.2016.06.017
dc.subject.halSciences du Vivant [q-bio]
bordeaux.journalCellular Signalling
bordeaux.page1470-1478
bordeaux.volume28
bordeaux.hal.laboratoriesBioingénierie Tissulaire (BioTis) - U1026*
bordeaux.issue10
bordeaux.institutionCNRS
bordeaux.institutionINSERM
bordeaux.institutionCHU de Bordeaux
bordeaux.institutionInstitut Bergonié
bordeaux.peerReviewedoui
hal.identifierinserm-02870967
hal.version1
hal.origin.linkhttps://hal.archives-ouvertes.fr//inserm-02870967v1
bordeaux.COinSctx_ver=Z39.88-2004&amp;rft_val_fmt=info:ofi/fmt:kev:mtx:journal&amp;rft.jtitle=Cellular%20Signalling&amp;rft.date=2016-10&amp;rft.volume=28&amp;rft.issue=10&amp;rft.spage=1470-1478&amp;rft.epage=1470-1478&amp;rft.eissn=0898-6568&amp;rft.issn=0898-6568&amp;rft.au=RIGOTHIER,%20Claire&amp;SALEEM,%20Moin%20Ahson&amp;BOURGET,%20Chantal&amp;MATHIESON,%20Peter%20William&amp;COMBE,%20Christian&amp;rft.genre=article


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