The γ2 subunit of GABAA receptors is a substrate for palmitoylation by GODZ

Cheryl A. Keller, Xu Yuan, Patrizia Panzanelli, Michelle L. Martin, Melissa Alldred, Marco Sassoè-Pognetto, Bernhard Lüscher

Research output: Contribution to journalArticlepeer-review

188 Scopus citations

Abstract

The neurotransmitter GABA activates heteropentameric GABAA receptors, which are composed mostly of α, β, and γ2 subunits. Regulated membrane trafficking and subcellular targeting of GABAA receptors is important for determining the efficacy of GABAergic inhibitory function. Of special interest is the γ2 subunit, which is mostly dispensable for assembly and membrane insertion of functional receptors but essential for accumulation of GABAA receptors at synapses. In a search for novel receptor trafficking proteins, we have used the SOS-recruitment system and isolated a Golgi-specific DHHC zinc finger protein (GODZ) as a novel γ2 subunit-interacting protein. GODZ is a member of the superfamily of DHHC cysteine-rich domain (DHHC-CRD) polytopic membrane proteins shown recently in yeast to represent palmitoyltransferases. GODZ mRNA is found in many tissues; however, in brain the protein is detected in neurons only and highly concentrated and asymmetrically distributed in the Golgi complex. GODZ interacts with a cysteine-rich 14-amino acid domain conserved specifically in the large cytoplasmic loop of γ1-3 subunits but not in other GABAA receptor subunits. Coexpression of GODZ and GABAA receptors in heterologous cells results in palmitoylation of the γ2 subunit in a cytoplasmic loop domain-dependent manner. Neuronal GABAA receptors are similarly palmitoylated. Thus, GODZ-mediated palmitoylation represents a novel posttranslational modification that is selective for γ subunit-containing GABAA receptor subtypes, a mechanism that is likely to be important for regulated trafficking of these receptors in the secretory pathway.

Original languageEnglish (US)
Pages (from-to)5881-5891
Number of pages11
JournalJournal of Neuroscience
Volume24
Issue number26
DOIs
StatePublished - Jun 30 2004

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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