FGD2, a CDC42-specific Exchange Factor Expressed by Antigen-presenting Cells, Localizes to Early Endosomes and Active Membrane Ruffles

Members of the Fgd (faciogenital dysplasia) gene family encode a group of critical guanine nucleotide exchange factors (GEFs), which, by specifically activating Cdc42, control cytoskeleton-dependent membrane rearrangements. In its first characterization, we find that FGD2 is expressed in antigen-pre...

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Bibliographic Details
Published in:The Journal of biological chemistry 2008-12, Vol.283 (49), p.34002-34012
Main Authors: Huber, Christoph, Mårtensson, Annica, Bokoch, Gary M., Nemazee, David, Gavin, Amanda L.
Format: Article
Language:English
Subjects:
Animals
Antigen Presentation
Antigen-Presenting Cells - metabolism
Blood Proteins - chemistry
Cell Membrane - metabolism
Chlorocebus aethiops
COS Cells
Endosomes - metabolism
Guanine Nucleotide Exchange Factors - genetics
Guanine Nucleotide Exchange Factors - metabolism
HeLa Cells
Humans
Macrophages - metabolism
Mice
Phosphoproteins - chemistry
Signal Transduction
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Summary:Members of the Fgd (faciogenital dysplasia) gene family encode a group of critical guanine nucleotide exchange factors (GEFs), which, by specifically activating Cdc42, control cytoskeleton-dependent membrane rearrangements. In its first characterization, we find that FGD2 is expressed in antigen-presenting cells, including B lymphocytes, macrophages, and dendritic cells. In the B lymphocyte lineage, FGD2 levels change with developmental stage. In both mature splenic B cells and immature bone marrow B cells, FGD2 expression is suppressed upon activation through the B cell antigen receptor. FGD2 has a complex intracellular localization, with concentrations found in membrane ruffles and early endosomes. Although endosomal localization of FGD2 is dependent on a conserved FYVE domain, its C-terminal pleckstrin homology domain mediates recruitment to membrane ruffles. FGD2 overexpression promotes the activation of Cdc42 and leads to elevated JNK1 activity in a Cdc42- but not Rac1-dependent fashion. These findings are consistent with a role of FGD2 in leukocyte signaling and vesicle trafficking in cells specialized to present antigen in the immune system.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M803957200