CaMKII Targets Specific SAP97 Splice Variant to Regulate AMPAR Activity

Strategic Insights -

Researchers have discovered a new mechanism by which Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) regulates the activity of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptors (AMPARs). CaMKII promotes the trafficking and activation of the GluR1 subunit of AMPARs during synaptic plasticity, and it achieves this by targeting a specific SAP97 splice variant. This variant, SAP97-I3I5, is essential for the interaction between SAP97 and A-kinase anchoring protein 79/150 (AKAP79/150), which in turn regulates GluR1 AMPAR activity. The study found that CaMKII phosphorylates SAP97-I3I5, preventing its interaction with AKAP79/150 and modulating AMPAR activity.

Key Takeaways:

  • CaMKII targets a specific SAP97 splice variant (SAP97-I3I5) to regulate AMPAR activity.
  • SAP97-I3I5 is essential for the interaction between SAP97 and AKAP79/150, which regulates GluR1 AMPAR activity.
  • CaMKII phosphorylates SAP97-I3I5, preventing its interaction with AKAP79/150 and modulating AMPAR activity.
  • The study provides new insight into protein-protein interactions and phosphorylation events required for normal regulation of glutamatergic synaptic transmission, learning, and memory.
  • CaMKII's role in regulating AMPAR activity has implications for understanding synaptic plasticity and the development of neurological disorders.
  • The study highlights the importance of specific SAP97 splice variants in regulating AMPAR activity and synaptic transmission.

Statistics:

  • Four alternative mRNA splice variants of SAP97 were identified in rat brain at postnatal day 21 ([1]).
  • CaMKII preferentially phosphorylates a full-length SAP97 and a GST fusion protein containing the I3 and I5 inserts (SAP97-I3I5 and GST-SH3-I3I5-GK, respectively) ([1]).
  • AKAP79/150 directly and specifically binds to GST-SH3-I3I5-GK, but CaMKII phosphorylation of GST-SH3-I3I5-GK prevents this interaction ([1]).

Sources:

[1] Nikandrova, Y.A., et al. (2010) Ca2+/calmodulin-dependent protein kinase II binds to and phosphorylates a specific SAP97 splice variant to disrupt association with AKAP79/150 and modulate alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptor (AMPAR) activity. Journal of Biological Chemistry, 285(2), 923-934.