XLG alpha(olf) was identified as a transcriptional variant of the heterotrimeric G protein, G alpha(olf). Previous work showed that XLG alpha(olf) couples with adenosine A2a receptor and dopamine D1 receptor in vitro. However, physiological functions of XLG alpha(olf) remain to be elucidated. In this study, we performed indirect immunofluorescence confocal analyses to examine the subcellular localization of XLG alpha(olf). With overexpression, surprisingly, many large endosomes resulted. We also observed that XLG alpha(olf) localizes at the Golgi apparatus. The N-terminal region of XLG alpha(olf) appears necessary for both endosome formation and the Golgi localization. The results indicate that XLG alpha(olf) and G alpha(olf) play distinctly separate roles. Moreover, XLG alpha(olf) colocalized with Rab3A and Rab8A, as well as partially with Rab11A, but not with other endocytotic endosomes. We could confirm the interaction between XLG alpha(olf) and Rab3A/Rab8A by co-immunoprecipitation experiments. Our study provides important clues toward understanding physiological functions of XLG alpha(olf). (C) 2009 Elsevier Inc. All rights reserved.