Gigaxonin (GAN)

GAN encodes a member of the cytoskeletal BTB/kelch (Broad-Complex, Tramtrack and Bric a brac) repeat family. (Kelch repeats are predicted to form a beta-propeller shape.) The encoded protein plays a role in neurofilament architecture and is mutated in giant axonal neuropathy.gigaxonin controls protein degradation and is essential for neuronal function and survival. gigaxonin binds to the ubiquitin-activating enzyme E1 through its amino-terminal BTB domain, while the carboxy-terminal kelch repeat domain interacts directly with the light chain (LC) of microtubule-associated protein-1B (MAP1B). Overexpression of gigaxonin leads to enhanced degradation of MAP1B-LC, which could be antagonized by proteasome inhibitors. Ablation of gigaxonin caused a substantial accumulation of MAP1B-LC in GAN-null neurons.