Direct Observation Demonstrates that Liprin-α Is Required for Trafficking of Synaptic Vesicles

Axonal transport is required for the elaboration and maintenance of synaptic morphology and function [1, 2]. Liprins are scaffolding proteins [3] important for synapse structure and electrophysiology [4]. A reported interaction with Kinesin-3 (Kif1a) suggested Liprinmay also be involved in axonal transport [5]. Here, at the light and ultrastructural levels, we discover aberrant accumulations of synaptic vesicle markers (Synaptotagmin and Synaptobrevin-GFP) and clearcore vesicles along Drosophila Liprin-a mutant axons. Analysis of presynaptic markers reveals reduced levels at Liprin-a synapses. Direct visualization of Synaptobrevin-GFP transport in living animals demonstrates a decrease in anterograde processivity in Liprin-a mutants but also an increase in retrograde transport initiation. Pull-down assays reveal that Liprininteracts with Drosophila Kinesin-1 (Khc) but not dynein. Together, these findings suggest that Liprinpromotes the delivery of synaptic material by a direct increase in kinesin processivity and an indirect suppression of dynein activation. This work is the first to use live observation in Drosophila mutants to demonstrate the role of a scaffolding protein in the regulation of bidirectional transport. It suggests the synaptic strength and morphology defects linked to Liprin-a [4, 6] may in part be due to a failure in the delivery of synaptic-vesicle precursors [7].