Episodic transport of protein aggregates achieves a positive size selectivity in aggresome formation.

ABSTRACT: Eukaryotic cells direct toxic misfolded proteins to various quality control pathways based on their chemical properties and aggregation status. Aggregated proteins are targeted to selective autophagy or specifically sequestered into the "aggresome", a perinuclear inclusion at the microtubule-organizing center (MTOC). However, the mechanism for selective aggresome recruitment remains unclear. To investigate this process, here we reconstitute MTOC-directed aggregate transport in Xenopus laevis egg extract using AgDD, a chemically inducible aggregation system. High-resolution single-particle tracking reveals that dynein-mediated aggregate transport is highly episodic, with average velocity positively correlating with aggregate size. Mechanistic modeling suggests that recurrent formation of th

SUBMITTER: Fang R 

PROVIDER: S-EPMC12373839 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature