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-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.
Huber
Christoph
C
Department of Immunology and Microbial Sciences, The Scripps Research Institute, La Jolla, California 92037, USA.
Mårtensson
Annica
A
Bokoch
Gary M
GM
Nemazee
David
D
Gavin
Amanda L
AL
D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000378:metabolism*; D001798:Blood Proteins / Q000737:chemistry; D019556:COS Cells; D002462:Cell Membrane / Q000378:metabolism*; D002522:Chlorocebus aethiops; D011992:Endosomes / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D010750:Phosphoproteins / Q000737:chemistry; D015398:Signal Transduction
D001798:Blood Proteins; C121389:FGD2 protein, human; C485666:Fgd2 protein, mouse; D020662:Guanine Nucleotide Exchange Factors; D010750:Phosphoproteins; C039077:platelet protein P47