Journal article
Epigenetic Regulation of Axonal Growth of Drosophila Pacemaker Cells by Histone Acetyltransferase Tip60 Controls Sleep
Genetics (Austin), v 192(4), pp 1327-1345
Dec 2012
PMID: 22982579
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Tip60 is a histone acetyltransferase (HAT) enzyme that epigenetically regulates genes enriched for neuronal functions through interaction with the amyloid precursor protein (APP) intracellular domain. However, whether Tip60-mediated epigenetic dysregulation affects specific neuronal processes
in vivo
and contributes to neurodegeneration remains unclear. Here, we show that Tip60 HAT activity mediates axonal growth of the
Drosophila
pacemaker cells, termed “small ventrolateral neurons” (sLNvs), and their production of the neuropeptide pigment-dispersing factor (PDF) that functions to stabilize
Drosophila
sleep–wake cycles. Using genetic approaches, we show that loss of Tip60 HAT activity in the presence of the Alzheimer’s disease-associated APP affects PDF expression and causes retraction of the sLNv synaptic arbor required for presynaptic release of PDF. Functional consequence of these effects is evidenced by disruption of the sleep–wake cycle in these flies. Notably, overexpression of Tip60 in conjunction with APP rescues these sleep–wake disturbances by inducing overelaboration of the sLNv synaptic terminals and increasing PDF levels, supporting a neuroprotective role for dTip60 in sLNv growth and function under APP-induced neurodegenerative conditions. Our findings reveal a novel mechanism for Tip60 mediated sleep–wake regulation via control of axonal growth and PDF levels within the sLNv-encompassing neural network and provide insight into epigenetic-based regulation of sleep disturbances observed in neurodegenerative diseases like Alzheimer’s disease.
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Details
- Title
- Epigenetic Regulation of Axonal Growth of Drosophila Pacemaker Cells by Histone Acetyltransferase Tip60 Controls Sleep
- Creators
- Sheila K Pirooznia - Department of Biology, Drexel University, Philadelphia, Pennsylvania 19104Kellie Chiu - Department of Biology, Drexel University, Philadelphia, Pennsylvania 19104May T Chan - Center for Sleep and Respiratory Neurobiology, University of Pennsylvania School of Medicine,Philadelphia, Pennsylvania 19104John E Zimmerman - Center for Sleep and Respiratory Neurobiology, University of Pennsylvania School of Medicine,Philadelphia, Pennsylvania 19104Felice Elefant - Department of Biology, Drexel University, Philadelphia, Pennsylvania 19104
- Publication Details
- Genetics (Austin), v 192(4), pp 1327-1345
- Publisher
- Genetics Society of America
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biology
- Web of Science ID
- WOS:000311960500010
- Scopus ID
- 2-s2.0-84870696884
- Other Identifier
- 991014877903104721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Genetics & Heredity