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Localization, proteomics, and metabolite profiling reveal a putative vesicular transporter for UDP-glucose
Cheng Qian1, Zhaofa Wu2,3, Rongbo Sun2,3
1School of Life Sciences, Tsinghua University, Beijing, China.
Elife
|July 16, 2021
Summary
Researchers identified novel vesicular neurotransmitter transporters (VNTs) by screening solute carrier (SLC) transporters. SLC35D3 was confirmed on synaptic vesicles, with UDP-glucose as its substrate, expanding knowledge of neurotransmitter diversity.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Vesicular neurotransmitter transporters (VNTs) are crucial for synaptic vesicle (SV) filling and neurotransmission.
- Identifying novel VNTs is essential for understanding neurotransmitter diversity and neuronal communication.
Purpose of the Study:
- To discover novel vesicular neurotransmitter transporters (VNTs) expressed on synaptic vesicles (SVs).
- To characterize the function and substrate specificity of newly identified VNTs.
Main Methods:
- Localization profiling of 361 solute carrier (SLC) transporters tagged with fluorescent proteins in neurons.
- Proteomics analysis of immunoisolated SVs to identify overlapping transporters.
- Ultrastructural analysis and metabolite profiling combined with radiolabeled substrate transport assays.
Main Results:
- Identified 40 potential VNT candidates from 361 SLC transporters.
- Seven transporters were found in common between localization profiling and SV proteomics.
- SLC35D3 was confirmed to localize to SVs, with UDP-glucose identified as its primary substrate.
Conclusions:
- The study successfully identified SLC35D3 as a novel SV transporter.
- UDP-glucose is a newly identified substrate for vesicular transport, expanding the known repertoire of chemical transmitters.
- These findings enhance understanding of the molecular diversity of neurotransmission and the role of SLC transporters.
Keywords:
UDP-glucosehumanmouseneuroscienceneurotransmitterssolute carriersynaptic vesiclestransporterMore Related Videos
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