Interaction between GRIP and liprin-alpha/SYD2 is required for AMPA receptor targeting.
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.
Wyszynski
Michael
M
Department of Neurobiology and Howard Hughes Medical Institute, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Kim
Eunjoon
E
Dunah
Anthone W
AW
Passafaro
Maria
M
Valtschanoff
Juli G
JG
Serra-Pagès
Carles
C
Streuli
Michel
M
Weinberg
Richard J
RJ
Sheng
Morgan
M
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism; D019556:COS Cells; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D010750:Phosphoproteins / Q000378:metabolism*; D017027:Protein Tyrosine Phosphatases; D051381:Rats; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2; D018091:Receptors, AMPA / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism; D013569:Synapses / Q000378:metabolism / Q000648:ultrastructure
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C491310:GRIP1 protein, human; C491308:Grip1 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; C490599:Ppfia4 protein, rat; D018091:Receptors, AMPA; D011956:Receptors, Cell Surface; C516772:PTPRF protein, human; D017027:Protein Tyrosine Phosphatases; C516774:Ptprf protein, rat; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2