Abstract
The class IIa histone deacetylase HDAC4 has been previously demonstrated to
play an essential role in brain development, learning and memory. However, the
molecular pathways through which it acts are unknown. HDAC4 undergoes
activity-dependent nucleocytoplasmic shuttling, and disruption of the balance of
nuclear and cytoplasmic HDAC4 has been identified as a factor in developmental
and neurodegenerative disorders. This project used Drosophila melanogaster as a
model to investigate the effects of altered subcellular distribution of HDAC4 on
neural development and memory formation through the overexpression of
Drosophila HDAC4 and wild-type human HDAC4 (hHDAC4), as well as nuclear-
and cytoplasm-localising mutants of hHDAC4 named 3SA and L175A,
respectively. This project has shown that nuclear but not cytoplasmic
HDAC4 impairs development and memory in Drosophila. Furthermore,
cytoplasmic HDAC4 may play a role in transcriptional regulation of neurons,
possibly regulation metabolic activity, suggesting that the activity-dependent
nucleocytoplasmic shuttling of HDAC4 may not be primarily to remove HDAC4
from the nucleus but instead to return HDAC4 to the cytoplasm.--Shortened abstract
Date
2019
Rights
The Author
Publisher
Massey University
Description
Embargoed until 16 May 2021