Cytosolic condensates rich in polyserine define subcellular sites of tau aggregation. Journal Article uri icon

Overview

abstract

  • Tau aggregates are a hallmark of multiple neurodegenerative diseases and can contain RNAs and RNA-binding proteins, including serine/arginine repetitive matrix protein 2 (SRRM2) and pinin (PNN). However, how these nuclear proteins mislocalize and their influence on the prion-like propagation of tau aggregates is unknown. We demonstrate that polyserine repeats in SRRM2 and PNN are necessary and sufficient for recruitment to tau aggregates. Moreover, we show tau aggregates preferentially grow in association with endogenous cytoplasmic assemblies-mitotic interchromatin granules and cytoplasmic speckles (CSs)-which contain SRRM2 and PNN. Polyserine overexpression in cells nucleates assemblies that are sites of tau aggregate growth. Further, modulating the levels of polyserine-containing proteins results in a corresponding change in tau aggregation. These findings define a specific protein motif, and cellular condensates, that promote tau aggregate propagation. As CSs form in induced pluripotent stem cell (iPSC) derived neurons under inflammatory or hyperosmolar stress, they may affect tau aggregate propagation in neurodegenerative disease.

publication date

  • January 17, 2023

has restriction

  • hybrid

Date in CU Experts

  • January 17, 2023 8:57 AM

Full Author List

  • Lester E; Van Alstyne M; McCann KL; Reddy S; Cheng LY; Kuo J; Pratt J; Parker R

author count

  • 8

Other Profiles

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

Additional Document Info

start page

  • e2217759120

volume

  • 120

issue

  • 3