Trafficking of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA) receptor subunit GluA2 from the endoplasmic reticulum is stimulated by a complex containing Ca2+/calmodulin-activated kinase II (CaMKII) and PICK1 protein and by release of Ca2+ from internal stores.
The GluA2 subunit of the AMPA receptor (AMPAR) dominantly blocks AMPAR Ca(2+) permeability, and its trafficking to the synapse regulates AMPAR-dependent synapse Ca(2+) permeability. Here we show that GluA2 trafficking from the endoplasmic reticulum (ER) to the plasma membrane of cultured hippocampal neurons requires Ca(2+) release from internal stores, the activity of Ca(2+)/calmodulin activated kinase II (CaMKII), and GluA2 interaction with the PDZ protein, PICK1. We show that upon Ca(2+) release from the ER via the IP3 and ryanodine receptors, CaMKII that is activated enters a complex that contains PICK1, dependent upon the PICK1 BAR (Bin-amphiphysin-Rvs) domain, and that interacts with the GluA2 C-terminal domain and stimulates GluA2 ER exit and surface trafficking. This study reveals a novel mechanism of regulation of trafficking of GluA2-containing receptors to the surface under the control of intracellular Ca(2+) dynamics and CaMKII activity.
From the Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York 10016.
Wei
W
Lu
From the Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York 10016.
Latika
L
Khatri
From the Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York 10016 edward.ziff@nyumc.org.
Edward B
EB
Ziff
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003598:Cytoskeletal Proteins; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D025461:Feedback, Physiological; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism*
D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D007295:Inositol Phosphates; D009687:Nuclear Proteins; C498298:PICK1 protein, rat; D018091:Receptors, AMPA; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; C104722:glutamate receptor ionotropic, AMPA 2; D002118:Calcium
BAR Domain; Ca2+/Calmodulin-dependent Protein Kinase II (CaMKII); Calcium; Endoplasmic Reticulum (ER); GluA2; Ionotropic Glutamate Receptor; PICK1; Trafficking; α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA Receptor, AMPAR)