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

• Published in: The Journal of biological chemistry Vol. 283; no. 49; pp. 34002 - 34012
• Main Authors: Huber, Christoph, Mårtensson, Annica, Bokoch, Gary M., Nemazee, David, Gavin, Amanda L.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 05.12.2008; American Society for Biochemistry and Molecular Biology
• 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
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M803957200

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.