The scaffold protein Cybr is required for cytokine-modulated trafficking of leukocytes in vivo

Vincenzo Coppola, Colleen A. Barrick, Sara Bobisse, Maria Cecilia Rodriguez-Galan, Michela Pivetta, Della Reynolds, O. M Zack Howard, Mary Ellen Palko, Pedro F. Esteban, Howard A. Young, Antonio Rosato, Lino Tessarollo

Research output: Contribution to journalArticlepeer-review


Trafficking and cell adhesion are key properties of cells of the immune system. However, the molecular pathways that control these cellular behaviors are still poorly understood. Cybr is a scaffold protein highly expressed in the hematopoietic/immune system whose physiological role is still unknown. In vitro studies have shown it regulates LFA-1, a crucial molecule in lymphocyte attachment and migration. Cybr also binds cytohesin-1, a guanine nucleotide exchange factor for the ARF GTPases, which affects actin cytoskeleton remodeling during cell migration. Here we show that expression of Cybr in vivo is differentially modulated by type 1 cytokines during lymphocyte maturation. In mice, Cybr deficiency negatively affects leukocytes circulating in blood and lymphocytes present in the lymph nodes. Moreover, in a Th1-polarized mouse model, lymphocyte trafficking is impaired by loss of Cybr, and Cybr-deficient mice with aseptic peritonitis have fewer cells than controls present in the peritoneal cavity, as well as fewer leukocytes leaving the bloodstream. Mutant mice injected with Moloney murine sarcoma/leukemia virus develop significantly larger tumors than wild-type mice and have reduced lymph node enlargement, suggesting reduced cytotoxic T-lymphocyte migration. Taken together, these data support a role for Cybr in leukocyte trafficking, especially in response to proinflammatory cytokines in stress conditions.

Original languageEnglish
Pages (from-to)5249-5258
Number of pages10
JournalMolecular and Cellular Biology
Issue number14
Publication statusPublished - Jul 2006

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology


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