Journal
MOLECULAR CELL
Volume 69, Issue 6, Pages 965-+Publisher
CELL PRESS
DOI: 10.1016/j.molcel.2018.02.004
Keywords
-
Categories
Funding
- Howard Hughes Medical Institute [045104] Funding Source: Medline
- NIGMS NIH HHS [R00 GM107355] Funding Source: Medline
- NIH HHS [S10 OD012254] Funding Source: Medline
- NINDS NIH HHS [R35 NS097974] Funding Source: Medline
Ask authors/readers for more resources
Under stress, certain eukaryotic proteins and RNA assemble to form membraneless organelles known as stress granules. The most well-studied stress granule components are RNA-binding proteins that undergo liquid-liquid phase separation (LLPS) into protein-rich droplets mediated by intrinsically disordered low-complexity domains (LCDs). Here we show that stress granules include proteasomal shuttle factor UBQLN2, an LCD-containing protein structurally and functionally distinct from RNA-binding proteins. In vitro, UBQLN2 exhibits LLPS at physiological conditions. Deletion studies correlate oligomerization with UBQLN2' s ability to phase-separate and form stress-induced cytoplasmic puncta in cells. Using nuclear magnetic resonance (NMR) spectroscopy, we mapped weak, multivalent interactions that promote UBQLN2 oligomerization and LLPS. Ubiquitin or polyubiquitin binding, obligatory for UBQLN2' s biological functions, eliminates UBQLN2 LLPS, thus serving as a switch between droplet and disperse phases. We postulate that UBQLN2 LLPS enables its recruitment to stress granules, where its interactions with ubiquitinated substrates reverse LLPS to enable shuttling of clients out of stress granules.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available