
St. Jude scientists (from left) Tanja Mittag, Ph.D., an assistant member of the Department of Structural Biology; Amandine Palud, student; and J. Paul Taylor, M.D., Ph.D., a Howard Hughes Medical Institute investigator and chair of the Department of Cell and Molecular Biology.
Ever noticed how oil and vinegar separate into droplets on a salad plate? St. Jude Children’s Research Hospital scientists have evidence that cells use the same process to stay organized and work properly.
The discovery answers a basic question of cell biology. The finding also shows a possible new way to treat devastating degenerative diseases like amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, frontotemporal dementia and inclusion body myopathy.
The mechanism is called liquid phase separation. It leads oil and vinegar to separate in salad dressing. St. Jude researchers found that under certain conditions the process may also prompt proteins with particular designs to condense into droplets inside cells. The droplets are likely the basis for temporary cell structures like stress granules. Many important cell functions take place in such structures.
Until now, the way stress granules form was not well understood. Neither was their connection to certain mutations in patients with ALS and related diseases.
This study provides that link. The findings have also fueled interest in developing treatments for diseases like ALS that work by blocking granule formation. J. Paul Taylor, MD, PhD, a Howard Hughes Medical Institute investigator and chair of the St. Jude Department of Cell and Molecular Biology, and Tanja Mittag, PhD, of the St. Jude Department of Structural Biology, led the research.
The study appears in the journal Cell.
Full citation:
Molliex A, Temirov J, Lee J, Coughlin M, Kanagaraj AP, Kim HJ, Mittag T, Taylor JP. Phase separation by low-complexity domains contributes to stress granule assembly and drives pathological fibrillization. Cell 163(1):123-33, 2015.
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