Localization, proteomics, and metabolite profiling reveal a putative vesicular transporter for UDP-glucose.
Elife
; 102021 07 16.
Article
en En
| MEDLINE
| ID: mdl-34269178
Vesicular neurotransmitter transporters (VNTs) mediate the selective uptake and enrichment of small-molecule neurotransmitters into synaptic vesicles (SVs) and are therefore a major determinant of the synaptic output of specific neurons. To identify novel VNTs expressed on SVs (thus identifying new neurotransmitters and/or neuromodulators), we conducted localization profiling of 361 solute carrier (SLC) transporters tagging with a fluorescent protein in neurons, which revealed 40 possible candidates through comparison with a known SV marker. We parallelly performed proteomics analysis of immunoisolated SVs and identified seven transporters in overlap. Ultrastructural analysis further supported that one of the transporters, SLC35D3, localized to SVs. Finally, by combining metabolite profiling with a radiolabeled substrate transport assay, we identified UDP-glucose as the principal substrate for SLC35D3. These results provide new insights into the functional role of SLC transporters in neurotransmission and improve our understanding of the molecular diversity of chemical transmitters.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Vesículas Sinápticas
/
Uridina Difosfato Glucosa
/
Transporte Biológico
/
Proteómica
/
Neuronas
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Elife
Año:
2021
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Reino Unido