Synapse maintenance is impacted by ATAT-2 tubulin acetyltransferase activity and the RPM-1 signaling hub.

Abstract

Synapse formation is comprised of target cell recognition, synapse assembly, and synapse maintenance. Maintaining established synaptic connections is essential for generating functional circuitry and synapse instability is a hallmark of neurodegenerative disease. While many molecules impact synapse formation generally, we know little about molecules that affect synapse maintenance in vivo. Using genetics and developmental time course analysis in <i>C.elegans</i>, we show that the α-tubulin acetyltransferase ATAT-2 and the signaling hub RPM-1 are required presynaptically to maintain stable synapses. Importantly, the enzymatic acetyltransferase activity of ATAT-2 is required for synapse maintenance. Our analysis revealed that RPM-1 is a hub in a genetic network composed of ATAT-2, PTRN-1 and DLK-1. In this network, ATAT-2 functions independent of the DLK-1 MAPK and likely acts downstream of RPM-1. Thus, our study reveals an important role for tubulin acetyltransferase activity in presynaptic maintenance, which occurs via the RPM-1/ATAT-2 pathway.