PT  - JOURNAL ARTICLE
AU  - Anna Grygoruk
AU  - Audrey Chen
AU  - Ciara A. Martin
AU  - Hakeem O. Lawal
AU  - Hao Fei
AU  - Gabriel Gutierrez
AU  - Traci Biedermann
AU  - Rod Najibi
AU  - Richard Hadi
AU  - Amit K. Chouhan
AU  - Niall P. Murphy
AU  - Felix E. Schweizer
AU  - Gregory T. Macleod
AU  - Nigel T. Maidment
AU  - David E. Krantz
TI  - The Redistribution of <em>Drosophila</em> Vesicular Monoamine Transporter Mutants from Synaptic Vesicles to Large Dense-Core Vesicles Impairs Amine-Dependent Behaviors
AID  - 10.1523/JNEUROSCI.0694-14.2014
DP  - 2014 May 14
TA  - The Journal of Neuroscience
PG  - 6924--6937
VI  - 34
IP  - 20
4099  - http://www.jneurosci.org/content/34/20/6924.short
4100  - http://www.jneurosci.org/content/34/20/6924.full
SO  - J. Neurosci.2014 May 14; 34
AB  - Monoamine neurotransmitters are stored in both synaptic vesicles (SVs), which are required for release at the synapse, and large dense-core vesicles (LDCVs), which mediate extrasynaptic release. The contributions of each type of vesicular release to specific behaviors are not known. To address this issue, we generated mutations in the C-terminal trafficking domain of the Drosophila vesicular monoamine transporter (DVMAT), which is required for the vesicular storage of monoamines in both SVs and LDCVs. Deletion of the terminal 23 aa (DVMAT-Δ3) reduced the rate of endocytosis and localization of DVMAT to SVs, but supported localization to LDCVs. An alanine substitution mutation in a tyrosine-based motif (DVMAT-Y600A) also reduced sorting to SVs and showed an endocytic deficit specific to aminergic nerve terminals. Redistribution of DVMAT-Y600A from SV to LDCV fractions was also enhanced in aminergic neurons. To determine how these changes might affect behavior, we expressed DVMAT-Δ3 and DVMAT-Y600A in a dVMAT null genetic background that lacks endogenous dVMAT activity. When expressed ubiquitously, DVMAT-Δ3 showed a specific deficit in female fertility, whereas DVMAT-Y600A rescued behavior similarly to DVMAT-wt. In contrast, when expressed more specifically in octopaminergic neurons, both DVMAT-Δ3 and DVMAT-Y600A failed to rescue female fertility, and DVMAT-Y600A showed deficits in larval locomotion. DVMAT-Y600A also showed more severe dominant effects than either DVMAT-wt or DVMAT-Δ3. We propose that these behavioral deficits result from the redistribution of DVMAT from SVs to LDCVs. By extension, our data suggest that the balance of amine release from SVs versus that from LDCVs is critical for the function of some aminergic circuits.