UNC-46 is required for trafficking of the vesicular GABA transporter

Kim Schuske, Mark T. Palfreyman, Shigeki Watanabe, Erik M. Jorgensen

Research output: Contribution to journalArticle

Abstract

Mutations in unc-46 in Caenorhabditis elegans cause defects in all behaviors that are mediated by GABA. Here we show that UNC-46 is a sorting factor that localizes the vesicular GABA transporter to synaptic vesicles. The UNC-46 protein is related to the LAMP (lysosomal associated membrane protein) family of proteins and is localized at synapses. In unc-46 mutants, the vesicular transporter is not found specifically in synaptic vesicles but rather is diffusely spread along the axon. Mislocalization of the transporter severely reduces the frequency of miniature currents, but the remaining currents are normal in amplitude. Because the number of synaptic vesicles is not depleted, it is likely that only a fraction of vesicles harbor the transporter in unc-46 mutants. Our data indicate that the transporter and UNC-46 have mutual roles in sorting. The vesicular GABA transporter recruits UNC-46 to synaptic vesicle precursors in the cell body, and UNC-46 sorts the transporter at the cell body and during endocytosis at the synapse.

Original languageEnglish (US)
Pages (from-to)846-853
Number of pages8
JournalNature Neuroscience
Volume10
Issue number7
DOIs
StatePublished - Jul 8 2007
Externally publishedYes

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Synaptic Vesicles
Synapses
Lysosome-Associated Membrane Glycoproteins
Caenorhabditis elegans
Endocytosis
gamma-Aminobutyric Acid
Axons
Proteins
Mutation
vesicular GABA transporter
Cell Body

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

UNC-46 is required for trafficking of the vesicular GABA transporter. / Schuske, Kim; Palfreyman, Mark T.; Watanabe, Shigeki; Jorgensen, Erik M.

In: Nature Neuroscience, Vol. 10, No. 7, 08.07.2007, p. 846-853.

Research output: Contribution to journalArticle

Schuske, Kim ; Palfreyman, Mark T. ; Watanabe, Shigeki ; Jorgensen, Erik M. / UNC-46 is required for trafficking of the vesicular GABA transporter. In: Nature Neuroscience. 2007 ; Vol. 10, No. 7. pp. 846-853.
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