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Tamalin may cooperate with Cybr in modulating leukocyte migration in vivo
Author(s) -
Coppola Vincenzo,
Tessarollo Lino
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.666.15
Subject(s) - pdz domain , microbiology and biotechnology , biology , immune system , cell migration , guanine nucleotide exchange factor , inflammation , cytoskeleton , in vivo , actin cytoskeleton , leukocyte trafficking , immunology , cell , gtpase , genetics , chemokine
Cybr (aka pscdbp , CASP or CBP ) is a scaffold protein that binds cythohesin‐1, a guanine nucleotide exchange factor for the ARF‐GTPases, which affects the actin cytoskeleton remodeling during cell migration. Indeed, we have shown in mouse that Cybr deficiency negatively affects the number of leukocytes circulating in blood and lymphocytes migrating to the lymph nodes especially in response to pro‐inflammatory cytokines in stress conditions. Notably, Cybr‐deficient mice show clear deficits of CTL‐mediated virus‐induced tumor rejection. Cybr is not expressed in the nervous system where its homolog Tamalin (aka Grasp ) is expressed the most. Tamalin too is a scaffold protein and shares with Cybr high homology at the PDZ and coiled‐coil domain suggesting common functions. Initially, Tamalin has been described as absent from the immune system. We show that Tamalin, although at low levels compared to Cybr, is expressed in the immune system. Tamalin is co‐expressed with Cybr in specific cell types suggesting a non‐redundant role for these two closely related proteins. The goal of this study is to investigate in vivo whether Tamalin deficiency affects leukocyte migration and augment defects due to Cybr deficiency. For this purpose, we have generated Tamalin deficient mice and subsequently Cybr/Tamalin double knock‐out mice. We have previously shown that Cybr has a role in cell migration in stress conditions. Here, we show that Tamalin defcient mice do not show any obvious deficit of leukocyte migration. However, preliminary results suggest that Tamalin deficiency may strengthen Cybr migration defect in specific conditions. Further investigation is needed to clarify how these two proteins modulate cell migration in vivo. This research is supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research.