PICK1

2022-05-05: reference:

PICK1 (Protein Kinase C interacting protein) #

• Targets the C-termini of GluR2, GluR3, and GluR4C - not found at inhibitory or “shaft” synapses, only spiny. Clustering of AMPA Receptors by the Synaptic PDZ Domain–Containing Protein PICK1.

• Not just merely responding to its action, it forms a complex with Protein Kinase Cα/C, helping target it to GluR2. It may have roles in insertion, but generally: PICK1 also reduces the plasma membrane levels of the GluR2 subunit PICK1 Targets Activated Protein Kinase Cα to AMPA Receptor Clusters in Spines of Hippocampal Neurons and Reduces Surface Levels of the AMPA-Type Glutamate Receptor Subunit 2, and mutations that prevent Ser880 phosphorylation reduce LTD (Glutamate receptor subunit 2 Serine 880 phosphorylation modulates synaptic transmission and mediates plasticity in CA1 pyramidal cells).

  • PICK1 Loss of Function Occludes Homeostatic Synaptic Scaling
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• Clustering of AMPA receptors by the synaptic PDZ domain-containing protein PICK1

  • Not positive what clustering means implies. Sounds quite important for pruning-type stuff.

• Phosphorylation of the AMPA Receptor Subunit GluR2 Differentially Regulates Its Interaction with PDZ Domain-Containing Proteins

  • Synaptic localization of PICK1 is quite variable, depending on culture conditions, and is regulated by PKC.
  • The PDZ domain of PICK1 is a type 1b PDZ domain, which binds to C-terminal PDZ ligands with a typical T/SXV motif, such as occurs in the C termini of Protein Kinase Cα, in which a hydroxyl group at position -2 is important for binding to PDZ domains
  • (I mean, naturally) it is colocalized with GluR2 at hippocampal neurons. Very little staining at excitatory synapses?
  • It frickin’ binds with GluR2 whether phosphorylated or not in vivo!

• It also has some interactions with mGluR, and DAT.

  • Functional Interaction between Monoamine Plasma Membrane Transporters and the Synaptic PDZ Domain–Containing Protein PICK1
    • Deletion of the PDZ binding site at the carboxyl terminus of DAT abolishes its association with PICK1 and impairs the localization of the transporter in neurons.

• PICK1 is implicated in organelle motility in an Arp2/3 complex–independent manner

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