The Machado-Joseph disease-associated form of ataxin-3 impacts dynamics of clathrin-coated pits.

Luciana K Rosselli-Murai, Jophin G Joseph, Iscia Lopes-Cendes, Allen P Liu, Marcelo J Murai

Cell biology international 2020 May

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Expansion above a certain threshold in the polyglutamine (polyQ) tract of ataxin-3 is the main cause of neurodegeneration in Machado-Joseph disease. Ataxin-3 contains an N-terminal catalytic domain, called Josephin domain, and a highly aggregation-prone C-terminal domain containing the polyQ tract. Recent work has shown that protein aggregation inhibits clathrin-mediated endocytosis (CME). However, the effects of polyQ expansion in ataxin-3 on CME have not been investigated. We hypothesize that the expansion of the polyQ tract in ataxin-3 could impact CME. Here, we report that both the wild-type and the expanded ataxin-3 reduce transferrin internalization and expanded ataxin-3 impacts dynamics of clathrin-coated pits (CCPs) by reducing CCP nucleation and increasing short-lived abortive CCPs. Since endocytosis plays a central role in regulating receptor uptake and cargo release, our work highlights a potential mechanism linking protein aggregation to cellular dysregulation. © 2020 International Federation for Cell Biology.

Citation

Luciana K Rosselli-Murai, Jophin G Joseph, Iscia Lopes-Cendes, Allen P Liu, Marcelo J Murai. The Machado-Joseph disease-associated form of ataxin-3 impacts dynamics of clathrin-coated pits. Cell biology international. 2020 May;44(5):1252-1259