Journal
TRENDS IN CELL BIOLOGY
Volume 29, Issue 4, Pages 308-322Publisher
ELSEVIER SCIENCE LONDON
DOI: 10.1016/j.tcb.2018.12.004
Keywords
-
Categories
Funding
- Ellison Medical Foundation
- American Federation for Aging Research
- Alzheimer's Association
- Life Extension Foundation
- ALS Association
- Department of Biochemistry and Biophysics Pilot Grant
- Target ALS
- Robert Packard Center for ALS Research at Johns Hopkins
- Office of the Assistant Secretary of Defense for Health Affairs [W81XWH-17-1-0237]
- NIH [T32GM008275, R01GM099836, R21NS090205]
Ask authors/readers for more resources
Nuclear-import receptors (NIRs) bind nuclear-localization signals (NLSs) of protein cargo in the cytoplasm and transport them into the nucleus. Here, we review advances establishing that NIRs also function in the cytoplasm to prevent and reverse functional and aberrant phase transitions of their cargo, including neurodegenerative disease-linked RNA-binding proteins (RBPs) with prion-like domains, such as TDP-43, FUS, hnRNPA1, and hnRNPA2. NIRs selectively extract cargo from condensed liquid phases thereby regulating functional phase separation. Consequently, NIRs sculpt cytoplasmic membraneless organelles and regulate cellular organization beyond their canonical role in nuclear import. Elevating NIR expression dissolves cytoplasmic RBP aggregates, restores functional RBPs to the nucleus, and rescues disease-linked RBP toxicity. Thus, NIRs could be leveraged therapeutically to restore RBP homeostasis and mitigate neurodegeneration.
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