title: RhoH participates in a multi-protein complex with the zinc finger protein kaiso that regulates both cytoskeletal structures and chemokine-induced T cells.
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.
authors: a Division of Hematology/Oncology, Boston Children's Hospital and the Dana-Farber Cancer Institute, Harvard Medical School , Boston , MA , USA.
authors: Akihisa
authors: A
authors: Mino
authors: b Department of Pediatric Hematology , Oncology and Stem Cell Transplantation, University Hospital Regensburg , Regensburg , Germany.
authors: Anja
authors: A
authors: Troeger
authors: a Division of Hematology/Oncology, Boston Children's Hospital and the Dana-Farber Cancer Institute, Harvard Medical School , Boston , MA , USA.
authors: Christian
authors: C
authors: Brendel
authors: a Division of Hematology/Oncology, Boston Children's Hospital and the Dana-Farber Cancer Institute, Harvard Medical School , Boston , MA , USA.
authors: Alan
authors: A
authors: Cantor
authors: a Division of Hematology/Oncology, Boston Children's Hospital and the Dana-Farber Cancer Institute, Harvard Medical School , Boston , MA , USA.
authors: Chad
authors: C
authors: Harris
authors: a Division of Hematology/Oncology, Boston Children's Hospital and the Dana-Farber Cancer Institute, Harvard Medical School , Boston , MA , USA.
authors: Marioara F
authors: MF
authors: Ciuculescu
authors: a Division of Hematology/Oncology, Boston Children's Hospital and the Dana-Farber Cancer Institute, Harvard Medical School , Boston , MA , USA.
authors: David A
authors: DA
authors: Williams
mesh_terms: D000199:Actins / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D018925:Chemokines / Q000494:pharmacology*; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D019169:Jurkat Cells; D011485:Protein Binding; D021381:Protein Transport / Q000187:drug effects; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry* / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016335:Zinc Fingers; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D000199:Actins; D018925:Chemokines; C447841:RhoH protein, human; D014157:Transcription Factors; C492254:ZBTB33 protein, human; D020741:rho GTP-Binding Proteins
keywords: Kaiso; RhoH; actin-cytoskeleton; chemokine; migration