HDAC6 is a Bruchpilot deacetylase that facilitates neurotransmitter release.

Autor:	Miskiewicz K; VIB Center for the Biology of Disease, Herestraat 49 bus 602, 3000 Leuven, Belgium; KU Leuven, Center for Human Genetics and Leuven Research Institute for Neuroscience and Disease (LIND), Herestraat 49 bus 602, 3000 Leuven, Belgium., Jose LE; VIB Center for the Biology of Disease, Herestraat 49 bus 602, 3000 Leuven, Belgium; KU Leuven, Center for Human Genetics and Leuven Research Institute for Neuroscience and Disease (LIND), Herestraat 49 bus 602, 3000 Leuven, Belgium., Yeshaw WM; VIB Center for the Biology of Disease, Herestraat 49 bus 602, 3000 Leuven, Belgium; KU Leuven, Center for Human Genetics and Leuven Research Institute for Neuroscience and Disease (LIND), Herestraat 49 bus 602, 3000 Leuven, Belgium., Valadas JS; VIB Center for the Biology of Disease, Herestraat 49 bus 602, 3000 Leuven, Belgium; KU Leuven, Center for Human Genetics and Leuven Research Institute for Neuroscience and Disease (LIND), Herestraat 49 bus 602, 3000 Leuven, Belgium., Swerts J; VIB Center for the Biology of Disease, Herestraat 49 bus 602, 3000 Leuven, Belgium; KU Leuven, Center for Human Genetics and Leuven Research Institute for Neuroscience and Disease (LIND), Herestraat 49 bus 602, 3000 Leuven, Belgium., Munck S; VIB Center for the Biology of Disease, Herestraat 49 bus 602, 3000 Leuven, Belgium; KU Leuven, Center for Human Genetics and Leuven Research Institute for Neuroscience and Disease (LIND), Herestraat 49 bus 602, 3000 Leuven, Belgium; VIB Bio Imaging Core, Herestraat 49 bus 602, 3000 Leuven, Belgium., Feiguin F; International Center for Genetic Engineering and Biotechnology, Padriciano 99, 34149 Trieste, Italy., Dermaut B; INSERM U744, Institut Pasteur de Lille, Université de Lille Nord de France, rue du Professeur Calmette 1, 59019 Lille, France; Center for Medical Genetics, Ghent University Hospital, De Pintelaan 185, 9000 Gent, Belgium., Verstreken P; VIB Center for the Biology of Disease, Herestraat 49 bus 602, 3000 Leuven, Belgium; KU Leuven, Center for Human Genetics and Leuven Research Institute for Neuroscience and Disease (LIND), Herestraat 49 bus 602, 3000 Leuven, Belgium. Electronic address: patrik.verstreken@cme.vib-kuleuven.be.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2014 Jul 10; Vol. 8 (1), pp. 94-102. Date of Electronic Publication: 2014 Jun 26.
DOI:	10.1016/j.celrep.2014.05.051
Abstrakt:	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. (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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