Journal
CELL REPORTS
Volume 15, Issue 7, Pages 1455-1466Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2016.04.045
Keywords
-
Categories
Funding
- NIH [ES020395, AG050471, NS089544, CA196631, NS091329, MD009205, AG042213]
- Alzheimer Association
- BrightFocus Foundation
- CurePSP Foundation
- CureAlzheimer Foundation [NS089544, ES20395, AG16574-17JP2]
- DOD [11811993]
Ask authors/readers for more resources
Dendritic mislocalization of microtubule associated protein tau is a hallmark of tauopathies, but the role of dendritic tau is unknown. We now report that tau interacts with the RNA-binding protein (RBP) TIA1 in brain tissue, and we present the brain-protein interactome network for TIA1. Analysis of the TIA1 interactome in brain tissue from wild-type (WT) and tau knockout mice demonstrates that tau is required for normal interactions of TIA1 with proteins linked to RNA metabolism, including ribosomal proteins and RBPs. Expression studies show that tau regulates the distribution of TIA1, and tau accelerates stress granule (SG) formation. Conversely, TIA1 knockdown or knockout inhibits tau misfolding and associated toxicity in cultured hippocampal neurons, while over-expressing TIA1 induces tau misfolding and stimulates neurodegeneration. Pharmacological interventions that prevent SG formation also inhibit tau pathophysiology. These studies suggest that the pathophysiology of tauopathy requires an intimate interaction with RNA-binding proteins.
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