Interaction between GRIP and liprin-α/SYD2 is required for AMPA receptor targeting

被引:201
作者
Wyszynski, M
Kim, E
Dunah, AW
Passafaro, M
Valtschanoff, JG
Serra-Pagès, C
Streuli, M
Weinberg, RJ
Sheng, M [1 ]
机构
[1] Massachusetts Gen Hosp, Dept Neurobiol, Boston, MA 02114 USA
[2] Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA
[3] Harvard Univ, Sch Med, Boston, MA 02114 USA
[4] MIT, Ctr Learning & Memory, RIKEN MIT Neurosci Res Ctr, Cambridge, MA 02139 USA
[5] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA
[6] Korea Adv Inst Sci & Technol, Dept Biol Sci, Taejon 305701, South Korea
[7] Univ N Carolina, Dept Cell Biol & Anat, Chapel Hill, NC 27599 USA
[8] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA
[9] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA
关键词
D O I
10.1016/S0896-6273(02)00640-2
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Interaction with the multi-PDZ protein GRIP is required for the synaptic targeting of AMPA receptors, but the underlying mechanism is unknown. We show that GRIP binds to the liprin-alpha/SYD2 family of proteins that interact with LAR receptor protein tyrosine phosphatases (LAR-RPTPs) and that are implicated in presynaptic development. In neurons, liprin-alpha and LAR-RPTP are enriched at synapses and coimmunoprecipitate with GRIP and AMPA receptors. Dominant-negative constructs that interfere with the GRIP-liprin interaction disrupt the surface expression and dendritic clustering of AMPA receptors in cultured neurons. Thus, by mediating the targeting of liprin/GRIP-associated proteins, liprin-alpha is important for postsynaptic as well as presynaptic maturation.
引用
收藏
页码:39 / 52
页数:14
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