Huntingtin-Associated Protein 1 (HAP1) Binds to a Trio-Like Polypeptide, with a rac1 Guanine Nucleotide Exchange Factor Domain

摘要: Huntington’s disease (HD) occurs when the widely expressed protein huntingtin contains an expanded glutamine repeat. The selective degeneration and neuronal morphologic abnormalities of HD may involve interactions with proteins that bind to huntingtin, such as HAP1. biological significance this interaction is unclear because neither HAP1 nor have significant homology known proteins. Therefore, we sought identify HAP1-binding Using yeast two-hybrid system, isolated a rat cDNA encoding part interacts HAP1, confirmed specificity using in vitro protein-binding assay. We called Duo it closely related human Trio but shorter. Northern blot analysis indicates brain-specific expression Duo. Human guanine nucleotide exchange factor (GEF) domain likely be rac1-specific, pleckstrin (PH) spectrin-like repeat units. These data support hypothesis involved vesicle trafficking cytoskeletal functions, raise possibility role for regulation ras-related signaling pathway.