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HDAC6 is a bruchpilot deacetylase that facilitates neurotransmitter release

(2014) CELL REPORTS. 8(1). p.94-102
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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.
Keywords
DROSOPHILA, ACTIVE ZONE, PROTEIN, TDP-43, ACETYLATION, CYTOMATRIX, COMPLEX, BINDING

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MLA
Miskiewicz, Katarzyna et al. “HDAC6 Is a Bruchpilot Deacetylase That Facilitates Neurotransmitter Release.” CELL REPORTS 8.1 (2014): 94–102. Print.
APA
Miskiewicz, K., Jose, L. E., Yeshaw, W. M., Valadas, J. S., Swerts, J., Munck, S., Feiguin, F., et al. (2014). HDAC6 is a bruchpilot deacetylase that facilitates neurotransmitter release. CELL REPORTS, 8(1), 94–102.
Chicago author-date
Miskiewicz, Katarzyna, Liya E Jose, Wondwossen M Yeshaw, Jorge S Valadas, Jef Swerts, Sebastian Munck, Fabian Feiguin, Bart Dermaut, and Patrik Verstreken. 2014. “HDAC6 Is a Bruchpilot Deacetylase That Facilitates Neurotransmitter Release.” Cell Reports 8 (1): 94–102.
Chicago author-date (all authors)
Miskiewicz, Katarzyna, Liya E Jose, Wondwossen M Yeshaw, Jorge S Valadas, Jef Swerts, Sebastian Munck, Fabian Feiguin, Bart Dermaut, and Patrik Verstreken. 2014. “HDAC6 Is a Bruchpilot Deacetylase That Facilitates Neurotransmitter Release.” Cell Reports 8 (1): 94–102.
Vancouver
1.
Miskiewicz K, Jose LE, Yeshaw WM, Valadas JS, Swerts J, Munck S, et al. HDAC6 is a bruchpilot deacetylase that facilitates neurotransmitter release. CELL REPORTS. 2014;8(1):94–102.
IEEE
[1]
K. Miskiewicz et al., “HDAC6 is a bruchpilot deacetylase that facilitates neurotransmitter release,” CELL REPORTS, vol. 8, no. 1, pp. 94–102, 2014.
@article{7185478,
  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.},
  author       = {Miskiewicz, Katarzyna and Jose, Liya E and Yeshaw, Wondwossen M and Valadas, Jorge S and Swerts, Jef and Munck, Sebastian and Feiguin, Fabian and Dermaut, Bart and Verstreken, Patrik},
  issn         = {2211-1247},
  journal      = {CELL REPORTS},
  keywords     = {DROSOPHILA,ACTIVE ZONE,PROTEIN,TDP-43,ACETYLATION,CYTOMATRIX,COMPLEX,BINDING},
  language     = {eng},
  number       = {1},
  pages        = {94--102},
  title        = {HDAC6 is a bruchpilot deacetylase that facilitates neurotransmitter release},
  url          = {http://dx.doi.org/10.1016/j.celrep.2014.05.051},
  volume       = {8},
  year         = {2014},
}

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