Synapse maintenance is impacted by ATAT-2 tubulin acetyltransferase activity and the RPM-1 signaling hub
- The Scripps Research Institute, United States
Abstract
Synapse formation is comprised of target 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 C. elegans, we show that the a-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.
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All data generated or analysed during this study are included in the manuscript and supporting files.
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Funding
National Institute of Neurological Disorders and Stroke (R01 NS072129)
- Brock Grill
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2019, Borgen et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Synapse maintenance is impacted by ATAT-2 tubulin acetyltransferase activity and the RPM-1 signaling hub
eLife 8:e44040.
https://doi.org/10.7554/eLife.44040
