Title: HDAC6 Is a Bruchpilot Deacetylase that Facilitates Neurotransmitter Release
Authors: Miskiewicz, Katarzyna *
Jose, Liya E *
Yeshaw, Wondwossen M
De Sousa Valadas, Jorge
Swerts, Jef
Munck, Sebastian
Feiguin, Fabian
Dermaut, Bart
Verstreken, Patrik # ×
Issue Date: Jul-2014
Publisher: CELL PRESS
Series Title: CELL REPORTS vol:8 issue:1 pages:94-102
Abstract: 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.
ISSN: 2211-1247
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
Laboratory of Neuronal Communication
* (joint) first author
× corresponding author
# (joint) last author

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