SNARE Protein Ykt6 Drives AMPAR Insertion at Synaptic Terminals During LTP

Ykt6 is a SNARE protein essential for vesicular fusion along the secretory pathway. It has been implicated in α-synuclein (αSyn) pathology and is critically involved in α-synuclein-dependent dementias. αSyn disrupts AMPA receptor (AMPAR) expression at synaptic terminals, which is key for long-term potentiation (LTP)—the cellular basis of memory and learning. AMPAR expression at synaptic terminals relies on the secretory pathway; however, the role of Ykt6 in LTP and its perturbation under αSyn pathological conditions remain unexplored. Here, we demonstrate that Ykt6 is highly expressed in the hippocampus of the mammalian brain, relocalizes to synaptic terminals during LTP, and regulates GluA1 surface expression. Moreover, we found that Ykt6 modulates the synaptic vesicular pools and dendritic arborization. Taken together, our findings establish Ykt6 as an essential SNARE for hippocampal neural function during LTP, with significant implications for α-synuclein-dependent dementias.