Protein aggregation can inhibit clathrin-mediated endocytosis by chaperone competition 1.0.0

However, CME was substantially reduced in cells con- taining Q82 aggregates (Fig. 1 B , arrows), with quantification of internalized transferrin fluorescence showing a 63 ± 11% reduction in aggregate-containing cells compared with cells expressing soluble Q19 or Q82 (Fig. 1 C ). PubMed:24706768

CME inhibition was also observed in cells containing aggregated forms of polyQ- expanded Htt exon 1 (Htt Q53); these cells exhibited 50 ± 15% reduced levels of internalized transferrin compared with cells with soluble Htt Q23 or Htt Q53 protein (Fig. S2 A–C ). PubMed:24706768

In contrast, there was a marked reduction in CME in neurons containing mutant Htt exon 1 Q73-CFP aggregates compared with nonexpressing cells (Fig. 5 B , Center ; quantification in Fig. 5 D ); PubMed:24706768

It has been proposed that such an imbalance may trigger the onset of many neurodegenerative diseases (10, 26), and recent studies report that polyglutamine (polyQ)-based aggregates can se- quester and inhibit the function of a low-abundance cochaper- one, Sis1p/DNAJB1, in protein degradation (27). PubMed:24706768

Previous studies have shown that ag- gregation of expanded polyQ negatively affects endocytosis in yeast and in human HEK 293 cells (34). PubMed:24706768