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 journalArticle

183 Citations (Scopus)

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

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Lipoylation
GABA-A Receptors
Cysteine
Membranes
Secretory Pathway
Zinc Fingers
Protein Subunits
Golgi Apparatus
Protein Transport
Post Translational Protein Processing
Synapses
gamma-Aminobutyric Acid
Neurotransmitter Agents
Membrane Proteins
Proteins
Yeasts
Neurons
Amino Acids
Messenger RNA
Brain

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Keller, Cheryl A. ; Yuan, Xu ; Panzanelli, Patrizia ; Martin, Michelle L. ; Alldred, Melissa ; Sassoè-Pognetto, Marco ; Lüscher, Bernhard. / The γ2 subunit of GABAA receptors is a substrate for palmitoylation by GODZ. In: Journal of Neuroscience. 2004 ; Vol. 24, No. 26. pp. 5881-5891.
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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.",
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Keller, CA, Yuan, X, Panzanelli, P, Martin, ML, Alldred, M, Sassoè-Pognetto, M & Lüscher, B 2004, 'The γ2 subunit of GABAA receptors is a substrate for palmitoylation by GODZ', Journal of Neuroscience, vol. 24, no. 26, pp. 5881-5891. https://doi.org/10.1523/JNEUROSCI.1037-04.2004

The γ2 subunit of GABAA receptors is a substrate for palmitoylation by GODZ. / Keller, Cheryl A.; Yuan, Xu; Panzanelli, Patrizia; Martin, Michelle L.; Alldred, Melissa; Sassoè-Pognetto, Marco; Lüscher, Bernhard.

In: Journal of Neuroscience, Vol. 24, No. 26, 30.06.2004, p. 5881-5891.

Research output: Contribution to journalArticle

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AU - Keller, Cheryl A.

AU - Yuan, Xu

AU - Panzanelli, Patrizia

AU - Martin, Michelle L.

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AU - Sassoè-Pognetto, Marco

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PY - 2004/6/30

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N2 - 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.

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Keller CA, Yuan X, Panzanelli P, Martin ML, Alldred M, Sassoè-Pognetto M et al. The γ2 subunit of GABAA receptors is a substrate for palmitoylation by GODZ. Journal of Neuroscience. 2004 Jun 30;24(26):5881-5891. https://doi.org/10.1523/JNEUROSCI.1037-04.2004