title: dTip60 HAT activity controls synaptic bouton expansion at the Drosophila neuromuscular junction.
abstract: BACKGROUND
  Histone acetylation of chromatin plays a key role in promoting the dynamic transcriptional responses in neurons that influence the neuroplasticity linked to cognitive ability, yet the specific histone acetyltransferases (HATs) that create such epigenetic marks remain to be elucidated.
  
  
  RESULTS
  Here we use the Drosophila neuromuscular junction (NMJ) as a well-characterized synapse model to identify HATs that control synaptic remodeling and structure. We show that the HAT dTip60 is concentrated both pre and post-synaptically within the NMJ. Presynaptic targeted reduction of dTip60 HAT activity causes a significant increase in synaptic bouton number that specifically affects type Is boutons. The excess boutons show a suppression of the active zone synaptic function marker bruchpilot, suggesting defects in neurotransmission function. Analysis of microtubule organization within these excess boutons using immunohistochemical staining to the microtubule associated protein futsch reveals a significant increase in the rearrangement of microtubule loop architecture that is required for bouton division. Moreover, α-tubulin acetylation levels of microtubules specifically extending into the terminal synaptic boutons are reduced in response to dTip60 HAT reduction.
  
  
  CONCLUSIONS
  Our results are the first to demonstrate a causative role for the HAT dTip60 in the control of synaptic plasticity that is achieved, at least in part, via regulation of the synaptic microtubule cytoskeleton. These findings have implications for dTip60 HAT dependant epigenetic mechanisms underlying cognitive function.
authors: Department of Biology, Drexel University, Philadelphia, Pennsylvania, United States of America.
authors: Jessica
authors: J
authors: Sarthi
authors: Felice
authors: F
authors: Elefant
mesh_terms: D000818:Animals; D003071:Cognition; D004330:Drosophila; D029721:Drosophila Proteins / Q000032:analysis / Q000378:metabolism* / Q000502:physiology; D051548:Histone Acetyltransferases / Q000032:analysis / Q000378:metabolism* / Q000502:physiology; D008870:Microtubules / Q000378:metabolism; D009469:Neuromuscular Junction / Q000166:cytology / Q000648:ultrastructure*; D017729:Presynaptic Terminals / Q000378:metabolism* / Q000648:ultrastructure; D013569:Synapses; D009435:Synaptic Transmission
chemical_list: D029721:Drosophila Proteins; D051548:Histone Acetyltransferases; C511056:Tip60 protein, Drosophila