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Distinct synaptic pools of DAPK1 differentially regulate activity-dependent synaptic CaMKII accumulation

Jonathan E Tullis1, K Ulrich Bayer1,2

  • 1Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.

Iscience
|May 22, 2023
PubMed

Insights

Death-associated protein kinase 1 (DAPK1) controls synaptic CaMKII movement essential for learning and memory. DAPK1 uses F-actin and GluN2B binding for synaptic localization, regulating synaptic plasticity during long-term depression (LTD).

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cell Biology

Background:

  • Synaptic plasticity, including long-term potentiation (LTP) and long-term depression (LTD), underlies learning and memory.
  • Ca2+/calmodulin-dependent protein kinase II (CaMKII) accumulation at synapses is crucial for LTP.
  • Suppression of CaMKII synaptic accumulation is required for LTD.

Purpose of the Study:

  • To investigate the mechanisms of DAPK1 localization to synapses.
  • To elucidate how DAPK1 regulates CaMKII synaptic movement during LTD.
  • To understand the role of DAPK1 binding modes in synaptic plasticity.

Main Methods:

  • Immunofluorescence and live-cell imaging to visualize protein localization.
  • Biochemical assays to study protein-protein interactions.
  • Genetic manipulation to assess the function of DAPK1 binding domains.

Main Results:

  • DAPK1 basal synaptic localization depends on F-actin.
  • LTD-specific retention of DAPK1 at synapses requires an additional binding mode, likely to GluN2B.
  • F-actin binding is necessary but not sufficient for suppressing CaMKII movement; it enables LTD-specific binding for CaMKII suppression.

Conclusions:

  • DAPK1 employs dual localization mechanisms for synaptic regulation.
  • F-actin and GluN2B binding cooperate to control synaptic CaMKII localization.
  • These DAPK1-mediated mechanisms are critical for regulating synaptic plasticity during LTD.
Keywords:
Cellular neuroscienceMolecular neuroscience

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