Protein aggregation can inhibit clathrin-mediated endocytosis by chaperone competition

• DOI: 10.1073/pnas.1321811111
• Publication Date: 2014-04-02T02:46:43Z
• Authors: Anan Yu; Yoko Shibata; Bijal Shah; Barbara Calamini; Donald C. Lo; Richard I. Morimoto
• Keywords: Internalization; Chaperone (clinical)

Significance The aggregation of mutant proteins is pathologically implicated in a large number neuropathies, including Huntington disease and ALS. Although the appearance protein aggregates known to sequester other proteins, how this results gain-of-function toxicity these diseases unclear. Here, we show that disease-associated causes reversible collapse clathrin-mediated endocytosis (CME) inhibits internalization membrane receptors affect neuronal function. CME inhibition occurs through aggregate-mediated sequestration molecular chaperone heat shock cognate 70, which essential for CME. We propose toxic “tug-of-war” between endogenous client available chaperones, leading multiple cellular processes neurodegeneration conformation diseases.