Different subcellular localizations for the related interferon-induced GTPases, MuGBP-1 and MuGBP-2: Implications for different functions?

The guanylate-binding proteins (GBPs) are a family of 65-67-kDa proteins in duced by both type I and type II interferons (IFN). Members of the GBP fami ly of GTPases are among the most abundant IFN-gamma -induced proteins. GBPs contain an unusual GTP binding site, which is consistent with GBP hydrolys is of GTP to both GDP and GMP. In addition, six of the eight known GBPs hav e a carboxy-terminal CaaX motif for the addition of isoprenyl lipids. Despi te their abundance, however, little is known about the biologic function or cellular location of GBPs. We report here on studies to localize both a ne wly identified murine GBP (MuGBP-2) and its closely related family member, MuGBP-1. In both IFN-treated macrophages and fibroblasts, MuGBP-2 is found in both a granular distribution throughout the cytoplasm and localized to v esicle populations of heterogeneous sizes. The localization of MuGBP-2 to v esicles is dependent on its isoprenylation. Despite a high degree of sequen ce identity and the presence of an identical CaaX sequence, MuGBP-1 has a v ery homogeneous cytoplasmic distribution and fails to localize to intracell ular vesicles. The different intracellular distribution of these two closel y related family members suggests differential function(s).