Toll-interacting protein pathway: degradation of an ubiquitin-binding protein.

The nine neurodegenerative disorders including Huntington disease (HD) are caused by the expansion of a trinucleotide CAG repeats (polyQ), which are located within the coding of the affected gene. Previous studies suggested that a gain of toxic function by polyQ repeats is widely thought to have a major role in pathogenesis. PolyQ-expanded htt induced ubiquitinated aggregates cause cell death in neuronal cells. Using a HD cellular model, we demonstrate that Tollip protects cells against the toxicity of polyQ-expanded htt and also protects cells from death (Oguro, Kubota, Shimizu, Ishiura, & Atomi, 2011). Tom1 which belongs to the VHS domain-containing protein family is also found to be directly binding to ubiquitin chains and Tollip (Katoh et al., 2004; Yamakami, Yoshimori, & Yokosawa, 2003). Tollip recruits misfolded protein to aggresome via late endosome. The cell system can be used to determine if your protein of interest is controlled under a part of Tollip pathway or not among other cell homeostatic systems: molecular chaperons, autophagy, and endoplasmic reticulum (ER)-associated degradation (ERAD). Tollip can be used for polyQ cell toxicity sensor by detecting microtubule-dependent trafficking and aggresome colocalization of aggregated protein.