It’s not just about physical attraction: Investigating the interaction between HDAC4 and Ankyrin2 in Drosophilamelanogaster neuronal function
Authors: Sarah Wilson; Silvia Schwartz; Helen Fitzsimons
Affiliation: School of Natural Sciences, Massey University, Palmerston North, New Zealand
Keywords: e. neuronal morphogenesis; j. epigenetics
Histone deacetylase 4 (HDAC4) is implicated in several neurodevelopmental and neurodegenerative diseases that involve deficits in memory and cognition. Increased expression of HDAC4 in the Drosophila brain impairs neuronal development and memory, thus Drosophila is an ideal model to investigate the molecular pathways through which HDAC4 acts. A recent genetic screen in Drosophila, for genes that interact in the same molecular pathway as HDAC4, identified the cytoskeletal adaptor Ankyrin2 (Ank2). Knockdown of Ank2 in the brain resulted in deficits in axon morphogenesis (Fisher’s, p < 0.01) with reduced elongation and guidance defects as well as significantly reduced dendritic branch lengths (Student’s t-test, p < 0.05), all of which are similar phenotypes to those resulting from increased expression of HDAC4.
HDAC4 contains a putative ankyrin-binding motif, suggesting that it may interact physically with Ank2, however no interaction was detected via co-immunoprecipitation. Further investigation revealed that expression of HDAC4 with a mutated ankyrin-binding motif retained the ability to interact genetically with Ank2 to synergistically impair photoreceptor development (ANOVA, p < 0.01), furthermore, this genetic interaction was dependent on the presence of HDAC4 in the nucleus. Together these data show that Ank2 and nuclear HDAC4 indirectly interact to regulate neuronal morphogenesis and function.