A function of huntingtin in guanine nucleotide exchange on Rab11.

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 Rab11, a critical GTPase in regulating membrane traffic from recycling endosomes to the plasma membrane. In huntingtin-null embryonic stem cells, the levels of Rab11 on membranes and nucleotide exchange activity on Rab11 were significantly reduced compared with normal embryonic stem cells. In brain membranes, an antibody against huntingtin immunoprecipitated a nucleotide exchange activity on Rab11 and huntingtin was coprecipitated with Rab11 in the presence of guanosine diphosphate. These data suggest a role for huntingtin in a complex that activates Rab11.