α-Synuclein kinetically regulates the nascent fusion pore dynamics
Rohith Kumar Nellikka, Bhavya R. Bhaskar, Kinjal Sanghrajka, Swapnali S. Patil, Debasis Das
Abstract
Significance The accumulation of nonfunctional α-synuclein (α-syn FL ) oligomers is the hallmark of Parkinson’s disease (PD), affecting millions of people worldwide. Although α-syn FL has a central role in PD, its cellular function is unclear until now. Understanding the normal function of α-syn FL is critical to envisage the molecular basis of abnormal cellular secretion under disease conditions. Previous studies indicated that it can regulate various steps of membrane fusion. Fusion pores are the crucial kinetic intermediates during membrane fusion, through which vesicular secretion occurs from different cell types. Here, we describe a function of α-syn FL in regulating the microsecond fusion pore transitions. This study offers an insight into how abnormal secretion occurs under pathological conditions in which nonfunctional α-syn FL accumulates.