HDAC6 Is a Bruchpilot Deacetylase that Facilitates Neurotransmitter Release

Presynaptic densities are specialized structures involved in synaptic vesicle tethering and neurotransmission; however, the mechanisms regulating their function remain understudied. In Drosophila, Bruchpilot is a major constituent of the presynaptic density that tethers vesicles. Here, we show that HDAC6 is necessary and sufficient for deacetylation of Bruchpilot. HDAC6 expression is also controlled by TDP-43, an RNA-binding protein deregulated in amyotrophic lateral sclerosis (ALS). Animals expressing TDP-43 harboring pathogenic mutations show increased HDAC6 expression, decreased Bruchpilot acetylation, larger vesicle-tethering sites, and increased neurotransmission, defects similar to those seen upon expression of HDAC6 and opposite to hdac6 null mutants. Consequently, reduced levels of HDAC6 or increased levels of ELP3, a Bruchpilot acetyltransferase, rescue the presynaptic density defects in TDP-43-expressing flies as well as the decreased adult locomotion. Our work identifies HDAC6 as a Bruchpilot deacetylase and indicates that regulating acetylation of a presynaptic release-site protein is critical for maintaining normal neurotransmission. publisher: Elsevier articletitle: HDAC6 Is a Bruchpilot Deacetylase that Facilitates Neurotransmitter Release journaltitle: Cell Reports articlelink: http://dx.doi.org/10.1016/j.celrep.2014.05.051 content_type: article copyright: Copyright © 2014 The Authors. Published by Elsevier Inc. ispartof: CELL REPORTS vol:8 issue:1 pages:94-102 ispartof: location:United States status: published