Alpha-Synuclein Fails to Form Aggregates in Endocytosis-Defective Fission Yeast Strains, ∆myo1 and ∆end4

Alpha-Synuclein (α-Syn) is a soluble neuronal protein whose aggregation is one of the hallmarks of Parkinson's disease (PD). We previously developed a fission yeast model of PD that recapitulates α-Syn aggregation upon high-level expression of human α-Syn. Here, we show that α-Syn aggregate formation in yeast requires Myo1 and End4 , proteins essential for the early steps of endocytosis. α-Syn expression levels in Δ <i>myo1</i> and <i>∆end4</i> cells were comparable to wild-type cells, suggesting that defects in endocytosis disrupt α-Syn aggregation. These findings highlight the critical role of endocytosis in α-Syn aggregation and PD pathology.