RhoH participates in a multi-protein complex with the zinc finger protein kaiso that regulates both cytoskeletal structures and chemokine-induced T cells
| Autor: | Akihisa Mino, Christian Brendel, David A. Williams, Marioara F. Ciuculescu, Chad E. Harris, Alan B. Cantor, Anja Troeger |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
rho GTP-Binding Proteins
0301 basic medicine T-Lymphocytes T cell GTPase Biology Biochemistry Jurkat cells Jurkat Cells 03 medical and health sciences 0302 clinical medicine Cell Movement Cell Adhesion medicine Humans Cell Shape Transcription factor Cytoskeleton Zinc finger ZAP70 T-cell receptor Zinc Fingers Cell Biology Actin cytoskeleton Research Papers Molecular biology Actins Cell biology Enzyme Activation Protein Transport 030104 developmental biology medicine.anatomical_structure Gene Knockdown Techniques 030220 oncology & carcinogenesis Chemokines Protein Binding Transcription Factors |
| Zdroj: | Small GTPases. 9:260-273 |
| ISSN: | 2154-1256 2154-1248 |
| DOI: | 10.1080/21541248.2016.1220780 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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