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- Title
Multiple Dileucine-like Motifs Direct VGLUT 1 Trafficking.
- Authors
Foss, Sarah M.; Haiyan Li; Santos, Magda S.; Edwards, Robert H.; Voglmaier, Susan M.
- Abstract
The vesicular glutamate transporters (VGLUTs) package glutamate into synaptic vesicles, and the two principal isoforms VGLUT 1 and VGLUT2 have been suggested to influence the properties of release. To understand how a VGLUT isoform might influence transmitter release, we have studied their trafficking and previously identified a dileucine-like endocytic motif in the C terminus of VGLUT1. Disruption of this motif impairs the activity-dependent recycling of VGLUT 1, but does not eliminate its endocytosis. We now report the identification of two additional dileucine-like motifs in the ? terminus of VGLUT 1 that are not well conserved in the other isoforms. In the absence of all three motifs, rat VGLUT1 shows limited accumulation at synaptic sites and no longer responds to stimulation. In addition, shRNA-mediated knockdown of clathrin adaptor proteins AP-1 and AP-2 shows that the C-terminal motif acts largely via AP-2, whereas the N-terminal motifs use AP-1. Without the C-terminal motif, knockdown of AP-1 reduces the proportion of VGLUT 1 that responds to stimulation. VGLUT1 thus contains multiple sorting signals that engage distinct trafficking mechanisms. In contrast to VGLUT1, the trafficking of VGLUT2 depends almost entirely on the conserved C-terminal dileucine-like motif: without this motif, a substantial fraction of VGLUT2 redistributes to the plasma membrane and the transporter's synaptic localization is disrupted. Consistent with these differences in trafficking signals, wild-type VGLUT 1 and VGLUT2 differ in their response to stimulation.
- Subjects
PHYSIOLOGICAL effects of leucine; VESICLE associated membrane protein; GLUTAMATE transporters; ORGAN trafficking; SYNAPTIC vesicles; CELLULAR signal transduction; NEURAL stimulation
- Publication
Journal of Neuroscience, 2013, Vol 33, Issue 26, p10647
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.5662-12.2013