کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2041673 1073169 2014 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
HDAC6 Is a Bruchpilot Deacetylase that Facilitates Neurotransmitter Release
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم کشاورزی و بیولوژیک علوم کشاورزی و بیولوژیک (عمومی)
پیش نمایش صفحه اول مقاله
HDAC6 Is a Bruchpilot Deacetylase that Facilitates Neurotransmitter Release
چکیده انگلیسی


• HDAC6 is necessary and sufficient for BRP deacetylation
• HDAC6 promotes the formation of larger presynaptic densities
• Different ALS-relevant pathways, ELP3 and TDP-43, converge on BRP deacetylation

SummaryPresynaptic 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.

Graphical AbstractFigure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 8, Issue 1, 10 July 2014, Pages 94–102
نویسندگان
, , , , , , , , ,