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      RhoH participates in a multi-protein complex with the zinc finger protein kaiso that regulates both cytoskeletal structures and chemokine-induced T cells

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          ABSTRACT

          RhoH is a haematopoietic -specific, GTPase-deficient Rho GTPase that plays an essential role in T lymphocyte development and haematopoietic cell migration. RhoH is known to interact with ZAP70 in T cell receptor (TCR) signaling and antagonize Rac GTPase activity. To further elucidate the molecular mechanisms of RhoH in T cell function, we carried out in vivo biotinylation and mass spectrometry analysis to identify new RhoH-interacting proteins in Jurkat T cells. We indentified Kaiso by streptavidin capture and confirmed the interaction with RhoH by co-immunoprecipitation. Kaiso is a 95 kDa dual-specific Broad complex, Trantrak, Bric-a-brac/Pox virus, Zinc finger (POZ-ZF) transcription factor that has been shown to regulate both gene expression and p120 catenin-associated cell-cell adhesions. We further showed that RhoH, Kaiso and p120 catenin all co-localize at chemokine-induced actin-containing cell protrusion sites. Using RhoH knockdown we demonstrated that Kaiso localization depends on RhoH function. Similar to the effect of RhoH deficiency, Kaiso down-regulation led to altered cell migration and actin-polymerization in chemokine stimulated Jurkat cells. Interestingly, RhoH and Kaiso also co-localized to the nucleus in a time-dependent fashion after chemokine stimulation and with T cell receptor activation where RhoH is required for Kaiso localization. Based on these results and previous studies, we propose that extracellular microenvironment signals regulate RhoH and Kaiso to modulate actin-cytoskeleton structure and transcriptional activity during T cell migration.

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          Author and article information

          Journal
          Small GTPases
          Small GTPases
          KSGT
          ksgt20
          Small GTPases
          Taylor & Francis
          2154-1248
          2154-1256
          2018
          31 August 2016
          : 9
          : 3
          : 260-273
          Affiliations
          [a ] Division of Hematology/Oncology, Boston Children's Hospital and the Dana-Farber Cancer Institute, Harvard Medical School , Boston, MA, USA
          [b ] Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, University Hospital Regensburg , Regensburg, Germany
          Author notes
          CONTACT David A. Williams DAWilliams@ 123456childrens.harvard.edu 300 Longwood Ave., Karp Family Research Laboratories 08125.3, Boston, MA 02115, USA

          Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/ksgt.

          Supplemental data for this article can be accessed on the publisher's website.

          Article
          PMC5927543 PMC5927543 5927543 1220780
          10.1080/21541248.2016.1220780
          5927543
          27574848
          5884f360-5e91-4d96-af2e-282d378c8c0b
          © 2016 Taylor & Francis
          History
          : 30 June 2016
          : 28 July 2016
          : 29 July 2016
          Page count
          Figures: 7, Tables: 0, References: 37, Pages: 14
          Funding
          Funded by: NIH
          Award ID: CA113969
          Funded by: Deutsche Forschungsgemeinschaft
          Award ID: TR 1005/1-1
          Funded by: NIH
          Award ID: DK098448
          This work was supported by NIH grants CA113969 (DAW) and DK098448 (AC) and Deutsche Forschungsgemeinschaft TR 1005/1-1 (AT).
          Categories
          Research Papers

          actin-cytoskeleton,Kaiso,migration,RhoH,chemokine
          actin-cytoskeleton, Kaiso, migration, RhoH, chemokine

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