Requirement of N-terminal cysteines of PSD-95 for PSD-95 multimerization and ternary complex formation, but not for binding to potassium channel Kv1.4

被引:73
作者
Hsueh, YP
Sheng, M [1 ]
机构
[1] Howard Hughes Med Inst, Boston, MA 02114 USA
[2] Massachusetts Gen Hosp, Dept Neurobiol, Boston, MA 02114 USA
[3] Harvard Univ, Sch Med, Boston, MA 02114 USA
关键词
D O I
10.1074/jbc.274.1.532
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The PSD-95 family of PSD-95/Discs large/ZO-1 (PDZ) domain-containing proteins plays a role in the clustering and localization of specific ion channels and receptors at synapses. Previous studies have shown that PSD-95 forms multimers through an N-terminal region (termed the N-segment) and that the multimerization of PSD-95 is critical for its ability to cluster Shaker-type potassium channel Kv1.4 in heterologous cells. We show here that the PSD-95 N-segment functions as a multimerization domain only when located at the N-terminal end of a heterologous protein. A pair of N-terminal cysteines, Cys(3) and Cys(5), is essential for the ability of PSD-95 to self-associate and to form cell surface clusters with Kv1.4. However, PSD-95 mutants lacking these cysteine residues retain their ability to associate with membranes and to bind to Kv1.4, Unlike wild type PSD-95, the cysteine mutant of PSD-95 cannot form a ternary complex with Kv1.4 and the cell adhesion molecule Fas-ciclin II. These results suggest that the N-terminal cysteines are essential for PSD-95 multimerization and that multimerization is required for simultaneous binding of multiple membrane protein ligands by PSD-95.
引用
收藏
页码:532 / 536
页数:5
相关论文
共 25 条
[1]   Cell signalling: MAGUK magic [J].
Anderson, JM .
CURRENT BIOLOGY, 1996, 6 (04) :382-384
[2]   Interaction of nitric oxide synthase with the postsynaptic density protein PSD-95 and alpha 1-syntrophin mediated by PDZ domains [J].
Brenman, JE ;
Chao, DS ;
Gee, SH ;
McGee, AW ;
Craven, SE ;
Santillano, DR ;
Wu, ZQ ;
Huang, F ;
Xia, HH ;
Peters, MF ;
Froehner, SC ;
Bredt, DS .
CELL, 1996, 84 (05) :757-767
[3]   Crystal structures of a complexed and peptide-free membrane protein-binding domain: Molecular basis of peptide recognition by PDZ [J].
Doyle, DA ;
Lee, A ;
Lewis, J ;
Kim, E ;
Sheng, M ;
MacKinnon, R .
CELL, 1996, 85 (07) :1067-1076
[4]   Disulfide-linked head-to-head multimerization in the mechanism of ion channel clustering by PSD-95 [J].
Hsueh, YP ;
Kim, E ;
Sheng, M .
NEURON, 1997, 18 (05) :803-814
[5]   Differential K+ channel clustering activity of PSD-95 and SAP97, two related membrane-associated putative guanylate kinases [J].
Kim, E ;
Sheng, M .
NEUROPHARMACOLOGY, 1996, 35 (07) :993-1000
[6]   Heteromultimerization and NMDA receptor-clustering activity of chapsyn-110, a member of the PSD-95 family of proteins [J].
Kim, E ;
Cho, KO ;
Rothschild, A ;
Sheng, M .
NEURON, 1996, 17 (01) :103-113
[7]   CLUSTERING OF SHAKER-TYPE K+ CHANNELS BY INTERACTION WITH A FAMILY OF MEMBRANE-ASSOCIATED GUANYLATE KINASES [J].
KIM, E ;
NIETHAMMER, M ;
ROTHSCHILD, A ;
JAN, YN ;
SHENG, M .
NATURE, 1995, 378 (6552) :85-88
[8]   SynGAP: a synaptic RasGAP that associates with the PSD-95/SAP90 protein family [J].
Kim, JH ;
Liao, DZ ;
Lau, LF ;
Huganir, RL .
NEURON, 1998, 20 (04) :683-691
[9]   Interaction of ion channels and receptors with PDZ domain proteins [J].
Kornau, HC ;
Seeburg, PH ;
Kennedy, MB .
CURRENT OPINION IN NEUROBIOLOGY, 1997, 7 (03) :368-373
[10]   DOMAIN INTERACTION BETWEEN NMDA RECEPTOR SUBUNITS AND THE POSTSYNAPTIC DENSITY PROTEIN PSD-95 [J].
KORNAU, HC ;
SCHENKER, LT ;
KENNEDY, MB ;
SEEBURG, PH .
SCIENCE, 1995, 269 (5231) :1737-1740