Exploring the Mitigation of TDP-43 Toxicity by Sis1 in Yeast

Abstract

Amyotrophic Lateral Sclerosis is a progressive neurodegenerative disease with a 100% fatality rate. Most cases have no known cause, with 5-10% of cases having a familial link. Currently there is no cure. Research has revealed that Tar DNA-binding Protein 43 cytoplasmic aggregates are involved in many cases of Amyotrophic Lateral Sclerosis. One possible mechanism for TDP-43 induced toxicity is that these aggregates are titrating away a molecular chaperone protein, Sis1, from the nucleus of the cell. Sis1 is important in the degradation of proteins, and without it, the cell would become non-viable. In order to examine the relationship between the two proteins, they were tagged with fluorescent proteins and examined for colocalization under fluorescent microscopy. However, while TDP-43 does appear to titrate Sis1 out of the nucleus, there was no evidence that the two proteins colocalized.