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

Mol Cell Biol. 2006 Jul;26(14):5249-58. doi: 10.1128/MCB.02473-05.


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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Movement
  • Cytokines / physiology*
  • Cytoskeletal Proteins / deficiency
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / physiology*
  • Gene Expression
  • Leukocytes / cytology
  • Leukocytes / immunology
  • Leukocytes / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Moloney murine sarcoma virus
  • Peritonitis / immunology
  • Peritonitis / pathology
  • Retroviridae Infections / immunology
  • Retroviridae Infections / pathology
  • Sarcoma, Experimental / immunology
  • Sarcoma, Experimental / pathology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / physiology
  • Tumor Virus Infections / immunology
  • Tumor Virus Infections / pathology


  • Cytokines
  • Cytoskeletal Proteins