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Cell Rep. 2016 May 17;15(7):1455-1466. doi: 10.1016/j.celrep.2016.04.045. Epub 2016 May 6.

Interaction of tau with the RNA-Binding Protein TIA1 Regulates tau Pathophysiology and Toxicity.

Author information

1
Department of Pharmacology & Experimental Therapeutics, Boston University School of Medicine, Boston, MA 02118, USA.
2
Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA.
3
Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
4
Department of Biochemistry and Molecular Pathology, University of Massachusetts Medical School, Shrewsbury, MA 01545, USA.
5
Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA 02115, USA.
6
Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40506, USA.
7
Department of Pathology and Laboratory Medicine, Boston University, Boston, MA 02118, USA.
8
Department of Pharmacology & Experimental Therapeutics, Boston University School of Medicine, Boston, MA 02118, USA; Department of Neurology, Boston University School of Medicine, Boston, MA 02118, USA. Electronic address: bwolozin@bu.edu.

Abstract

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 overexpressing 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.

PMID:
27160897
PMCID:
PMC5325702
DOI:
10.1016/j.celrep.2016.04.045
[Indexed for MEDLINE]
Free PMC Article

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