Trafficking of AMPA Receptor Subunit GluA2 from the Endoplasmic Reticulum is Stimulated by a Complex Containing CaMKII and PICK1 and by Release of Ca2+ from Internal Stores [Signal Transduction]

May 15th, 2014 by Lu, W., Khatri, L., Ziff, E. B.

The GluA2 subunit of the AMPA receptor (AMPAR) dominantly blocks AMPAR Ca2+ permeability, and its trafficking to the synapse regulates AMPAR-dependent synapse Ca2+ permeability. Here we show that GluA2 trafficking from the endoplasmic reticulum (ER) to the plasma membrane of cultured hippocampal neurons requires Ca2+ release from internal stores, the activity of Ca2+/calmodulin activated kinase II (CaMKII) and GluA2 interaction with the PDZ protein, PICK1. We show that upon Ca2+ 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 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 Ca2+ dynamics and CaMKII activity.
  • Posted in Journal of Biological Chemistry, Publications
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