 |
The Journal of Neuroscience, December 6, 2006, 26(49):12758-12768; doi:10.1523/JNEUROSCI.4214-06.2006
Previous Article | Next Article 
Cellular/Molecular
GODZ-Mediated Palmitoylation of GABAA Receptors Is Required for Normal Assembly and Function of GABAergic Inhibitory Synapses
Cheng Fang,1,2,3
Lunbin Deng,1,3
Cheryl A. Keller,1,2,3
Masaki Fukata,5
Yuko Fukata,5
Gong Chen,1,3 and
Bernhard Lüscher1,2,3,4
1Department of Biology, 2Department of Biochemistry and Molecular Biology, and 3Penn State Neuroscience Institute, Pennsylvania State University, University Park, Pennsylvania 16802, 4Department of Psychiatry, Pennsylvania State University, Hershey, Pennsylvania 17033, and 5Laboratory of Genomics and Proteomics, National Institute for Longevity Sciences, Aichi 474-8522, Japan
Correspondence should be addressed to Dr. Bernhard Luscher, Department of Biology and Biochemistry and Molecular Biology, Penn State Neuroscience Institute, Pennsylvania State University, 301 Life Sciences Building, University Park, PA 16802. Email: BXL25{at}psu.edu
Golgi-specific DHHC (Asp-His-His-Cys) zinc finger protein (GODZ) is a DHHC family palmitoyl acyltransferase that is implicated in palmitoylation and regulated trafficking of diverse substrates that function either at inhibitory or excitatory synapses. Of particular interest is the 2 subunit of GABAA receptors, which is required for targeting these receptors to inhibitory synapses. Here, we report that GODZ and, to a lesser extent, its close paralog sertoli cell gene with a zinc finger domain-ß (SERZ-ß) are the main members of the DHHC family of enzymes that are able to palmitoylate the 2 subunit in heterologous cells. Yeast two-hybrid and colocalization assays in human embryonic kidney 293T (HEK293T) cells indicate that GODZ and SERZ-ß show indistinguishable palmitoylation-dependent interaction with the 2 subunit. After coexpression in HEK293T cells, they form homomultimers and heteromultimers, as shown by coimmunoprecipitation and in vivo cross-linking experiments. Analyses in neurons transfected with dominant-negative GODZ (GODZC157S) or plasmid-based GODZ-specific RNAi indicate that GODZ is required for normal accumulation of GABAA receptors at synapses, for normal whole-cell and synaptic GABAergic inhibitory function and, indirectly, for GABAergic innervation. Unexpectedly, GODZ was found to be dispensable for normal postsynaptic AMPA receptor-mediated glutamatergic transmission. We conclude that GODZ-mediated palmitoylation of GABAA receptors and possibly other substrates contributes selectively to the formation and normal function of GABAergic inhibitory synapses.
Key words: trafficking; synaptogenesis; inhibitory synapses; palmitoylation; DHHC-CRD proteins; GABAA receptors
Received May 26, 2006;
revised Oct. 25, 2006;
accepted Oct. 27, 2006.
Correspondence should be addressed to Dr. Bernhard Luscher, Department of Biology and Biochemistry and Molecular Biology, Penn State Neuroscience Institute, Pennsylvania State University, 301 Life Sciences Building, University Park, PA 16802. Email: BXL25{at}psu.edu
This article has been cited by other articles:

|
 |

|
 |
 
J. Greaves, C. Salaun, Y. Fukata, M. Fukata, and L. H. Chamberlain
Palmitoylation and Membrane Interactions of the Neuroprotective Chaperone Cysteine-string Protein
J. Biol. Chem.,
September 5, 2008;
283(36):
25014 - 25026.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Patrizi, B. Scelfo, L. Viltono, F. Briatore, M. Fukaya, M. Watanabe, P. Strata, F. Varoqueaux, N. Brose, J.-M. Fritschy, et al.
Synapse formation and clustering of neuroligin-2 in the absence of GABAA receptors
PNAS,
September 2, 2008;
105(35):
13151 - 13156.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. D. Munday and J. A. Lopez
Posttranslational Protein Palmitoylation: Promoting Platelet Purpose
Arterioscler. Thromb. Vasc. Biol.,
July 1, 2007;
27(7):
1496 - 1499.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. C. Earnheart, C. Schweizer, F. Crestani, T. Iwasato, S. Itohara, H. Mohler, and B. Luscher
GABAergic Control of Adult Hippocampal Neurogenesis in Relation to Behavior Indicative of Trait Anxiety and Depression States
J. Neurosci.,
April 4, 2007;
27(14):
3845 - 3854.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|