Grygoruk, A., Fei, H., Daniels, R.W., Miller, B.R., Diantonio, A., Krantz, D.E. (2010). A Tyrosine-based Motif Localizes a Drosophila Vesicular Transporter to Synaptic Vesicles in Vivo. J. Biol. Chem. 285(10): 6867--6878.
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Vesicular neurotransmitter transporters must localize to synaptic vesicles (SVs) to allow regulated neurotransmitter release
at the synapse. However, the signals required to localize vesicular proteins to SVs in vivo remain unclear. To address this
question we have tested the effects of mutating proposed trafficking domains in Drosophila orthologs of the vesicular monoamine
and glutamate transporters, DVMAT-A and DVGLUT. We show that a tyrosine-based motif (YXXY) is important both for DVMAT-A internalization
from the cell surface in vitro, and localization to SVs in vivo. In contrast, DVGLUT deletion mutants that lack a putative
C-terminal trafficking domain show more modest defects in both internalization in vitro and trafficking to SVs in vivo. Our
data show for the first time that mutation of a specific trafficking motif can disrupt localization to SVs in vivo and suggest
possible differences in the sorting of VMATs versus VGLUTs to SVs at the synapse.
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