A function of huntingtin in guanine nucleotide exchange on RabII

Huntingtin is ubiquitously expressed and enriched in the brain. Deletion of the huntingtin gene in mice is lethal during early embryonic development. The function of huntingtin is, however, not clear. Here, we report that huntingtin is important for the function of RabII, a critical GTPase in regulating membrane traffic from recycling endosomes to the plasma membrane. In huntingtinnull embryonic cells, the levels of RabII on membranes nucleotide exchange activity on RabII were significantly reduced compared with normal embryonic stem cells. In brain membranes, an antibody against huntingtin immunoprecipitated a nucleoticle exchange activity on RabII and huntingtin was coprecipitated with RabII in the presence of guanosine diphosphate. These data suggest a role for huntingtin in a complex that activates RabII. NeuroReport 19:1643-1647 (C) 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins.