It is interesting that an alternative GNAT domain protein, MEC-17, was shown to acetylate tubulin in different systems, including nematodes, zebrafish, and ciliates ( Akella et al., 2010); in addition, an acetyltransferase complex, ARD1-NAT1, that can acetylate tubulin in vitro has been found associated with tubulin in developing dendrites of cultured hippocampal neurons and was shown to regulate dendritic outgrowth in vitro ( Ohkawa et al., 2008). Thus, alternative tubulin acetyltransferases that regulate

neuronal morphology have been identified. In a search of alternative cytoplasmic ELP3 selleck chemicals llc targets, we identified BRP, a large cytoskeletal-like protein that decorates the active zone where synaptic vesicles fuse with the membrane. We provide several lines of evidence that ELP3 acts to acetylate BRP at the Drosophila NMJ. First, ELP3 is present at NMJ boutons, localizing the enzyme in close proximity to BRP. Second, acetylated lysine levels that overlap with BRPNC82 labeling at the NMJ are reduced in elp3 mutants. Similarly, BRP-associated acetylated lysine levels detected by western blotting are reduced in elp3 mutants. Third, immunoprecipitated BRP is efficiently acetylated by purified ELP3 in vitro. Without excluding other substrates, our data mTOR signaling pathway indicate that ELP3 is necessary and sufficient to acetylate BRP. BRP is indeed an excellent candidate to undergo this modification as it contains numerous

coiled-coil motifs that were recently

shown to be ideal acetylation substrates ( Choudhary et al., 2009). Individual BRP strands organize into parasol-like structures, with their N termini facing the plasma membrane, contacting calcium channels, and their C termini extending into the cytoplasm capturing synaptic vesicles (Fouquet et al., 2009, Hallermann et al., 2010b and Jiao et al., 2010). While mutations that affect BRP transport to synapses or assembly of T bars at active zones exist, our data indicate that these processes are not affected in elp3 mutants. Unlike SRPK79D mutants ( Johnson et al., 2009 and Nieratschker Sclareol et al., 2009), BRPNC82 does not accumulate in elp3 mutant motor neurons (data not shown), suggesting normal axonal transport. In addition, in contrast to rab3 mutants ( Graf et al., 2009), the number of T bars per synaptic area is not different in controls and elp3 mutants. Our analyses also identified a postsynaptic role for elp3 in regulating glutamate receptor subunit IIA abundance in muscles at NMJs and, thus, mEJC amplitude; however, unlike ELP3′s neuronal function, we show that this role of ELP3 is not critical for viability, as muscular expression of the protein does not rescue elp3-associated lethality. Nonetheless, by regulating postsynaptic receptor field size, ELP3 may also modulate neuronal communication. We present evidence that this defect is regulated in muscle cells independently of the presynaptic role of ELP3.