Our trainees review webinars in their given fields and share abstracts to help colleagues outside their discipline make an informed choice about watching them. As our program bridges diverse disciplines, these abstracts are beneficial for our own group in helping one another gain key knowledge in each other’s fields. We are happy to share these here for anyone else who may find them helpful.
Stress granules: Deciphering the connections to neurodegeneration
Dorothee Dormann, Benjamin Wolozin
Watch on the WorkCast website >>
Summary and Analysis by Miles Norsworthy:
Stress granules are phase separated clumps of RNA and protein lacking a membrane that are typically thought of as the cell compensating due to some sort of stressor. However, these granules may potentially lead to cell death and neurodegeneration. Drs. Dormann and Wolozin explore the complicated pathways of these granules in relation to neurodegeneration.
Dr. Dormann’s presentation focuses on the proteins TDP-43 and FUS. Typically found within the nucleus these proteins migrate to the cytoplasm of neurons in those suffering from ALS and frontotemporal dementia (FTD). Common in familial cases of ALS are point mutations within the region of TDP-43. Dormann’s lab discovered that these mutations prevent the nuclear localization of TDP-43 and FUS.
However, the failure of FUS localization to the nucleus does not immediately lead to pathogenic clustering until the neurons undergo some type of stress. Additionally, FUS alone in vitro will form clusters given enough time (in the span of days) and a high enough concentration. Ultimately, the lab discovered that the nuclear import receptor TNP01 binds to FUS and functions as a “holdase” that prevents the clumping of FUS.
Dr. Wolozin’s lab focuses on the interaction of Tau with stress granules. Their general hypothesis is that Tau alters the translational response to stress by interacting with stress granules. They show that in mice with mutated Tau knock downs of other proteins in stress granules lead to longer lives in mutated mice. Additionally, Wolozin shows that oligomeric Tau is more toxic to cells compared to fibrillar forms and that the nature of stress granule composition varies based upon the cellular stress being acute vs. chronic.