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

被引:199
作者
Keller, CA
Yuan, X
Panzanelli, P
Martin, ML
Alldred, M
Sassoè-Pognetto, M
Lüscher, B
机构
[1] Penn State Univ, Dept Biol, Mueller Lab 208, University Pk, PA 16802 USA
[2] Penn State Univ, Dept Biochem, University Pk, PA 16802 USA
[3] Penn State Univ, Dept Mol Biol, University Pk, PA 16802 USA
[4] Univ Turin, Dept Anat Phamracol & Forens Med, I-10126 Turin, Italy
[5] Univ Turin, Rita Levi Montalcini Ctr Brain Repair, I-10126 Turin, Italy
关键词
PAT; trafficking; exocytosis; palmitoyltransferase; SERZ-beta; GABA;
D O I
10.1523/JNEUROSCI.1037-04.2004
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The neurotransmitter GABA activates heteropentameric GABA(A) receptors, which are composed mostly of alpha, beta, and gamma2 subunits. Regulated membrane trafficking and subcellular targeting of GABA(A) receptors is important for determining the efficacy of GABAergic inhibitory function. Of special interest is the gamma2 subunit, which is mostly dispensable for assembly and membrane insertion of functional receptors but essential for accumulation of GABA(A) 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 gamma2 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 gamma1-3 subunits but not in other GABA(A) receptor subunits. Coexpression of GODZ and GABA(A) receptors in heterologous cells results in palmitoylation of the gamma2 subunit in a cytoplasmic loop domain-dependent manner. Neuronal GABA(A) receptors are similarly palmitoylated. Thus, GODZ-mediated palmitoylation represents a novel posttranslational modification that is selective for gamma subunit-containing GABA(A) receptor subtypes, a mechanism that is likely to be important for regulated trafficking of these receptors in the secretory pathway.
引用
收藏
页码:5881 / 5891
页数:11
相关论文
共 63 条
[1]  
[Anonymous], 1988, Antibodies: A Laboratory Manual
[2]   Analysis and identification of protein-protein interactions using protein recruitment systems [J].
Aronheim, A ;
Karin, M .
APPLICATIONS OF CHIMERIC GENES AND HYBRID PROTEINS, PT C, 2000, 328 :47-59
[3]   Postsynaptic clustering of γ-aminobutyric acid type A receptors by the γ3 subunit in vivo [J].
Baer, K ;
Essrich, C ;
Benson, JA ;
Benke, D ;
Bluethmann, H ;
Fritschy, JM ;
Lüscher, B .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (22) :12860-12865
[4]   Erf2, a novel gene product that affects the localization and palmitoylation of Ras2 in Saccharomyces cerevisiae [J].
Bartels, DJ ;
Mitchell, DA ;
Dong, XW ;
Deschenes, RJ .
MOLECULAR AND CELLULAR BIOLOGY, 1999, 19 (10) :6775-6787
[5]  
Bateman A, 2004, NUCLEIC ACIDS RES, V32, pD138, DOI [10.1093/nar/gkp985, 10.1093/nar/gkr1065, 10.1093/nar/gkh121]
[6]   GABA(A) receptor subtypes differentiated by their gamma-subunit variants: Prevalence, pharmacology and subunit architecture [J].
Benke, D ;
Honer, M ;
Michel, C ;
Mohler, H .
NEUROPHARMACOLOGY, 1996, 35 (9-10) :1413-1423
[7]   Pharmacology of recombinant γ-aminobutyric acida receptors rendered diazepam-insensitive by point-mutated α-subunits [J].
Benson, JA ;
Löw, K ;
Keist, R ;
Mohler, H ;
Rudolph, U .
FEBS LETTERS, 1998, 431 (03) :400-404
[8]  
Bernstein Leah S, 2004, Methods Mol Biol, V237, P195
[9]   BIOCHEMICAL-CHARACTERIZATION OF A PALMITOYL ACYLTRANSFERASE ACTIVITY THAT PALMITOYLATES MYRISTOYLATED PROTEINS [J].
BERTHIAUME, L ;
RESH, MD .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (38) :22399-22405
[10]   The on-off story of protein palmitoylation [J].
Bijlmakers, MJ ;
Marsh, M .
TRENDS IN CELL BIOLOGY, 2003, 13 (01) :32-42