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Presynaptic development is controlled by the core active zone proteins CAST/ELKS.

Tamara Radulovic1, Wei Dong2, R Oliver Goral1

  • 1Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, IA, 52242, USA.

The Journal of Physiology
|April 19, 2020
PubMed
Summary

CAST/ELKS proteins promote presynaptic growth and suppress active zone expansion during development. Despite altering calcium channel levels, their absence does not impact synaptic transmission in the calyx of Held.

Keywords:
active zonecalcium channelcalyx of Heldneuronal circuitsynapsesynapse formation

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Developmental Biology

Background:

  • Presynaptic active zone (AZ) proteins, like CAST/ELKS, have complex roles in neuronal development.
  • Understanding CAST/ELKS function in vivo during early circuit maturation is crucial.

Purpose of the Study:

  • To investigate the roles of CAST/ELKS in glutamatergic synapse development and presynaptic function.
  • To analyze the impact of CAST/ELKS loss on the calyx of Held terminal during early circuit maturation.

Main Methods:

  • Utilized CAST knockout (KO) and ELKS conditional KO (CKO) mice.
  • Performed morphological analysis using confocal microscopy.
  • Assessed AZ ultrastructure and synaptic function via patch-clamp recordings.

Main Results:

  • CAST/ELKS deletion reduced calyx surface area and volume but increased AZ size.
  • Loss of CAST/ELKS decreased all presynaptic CaV 2 channel subtypes and their currents.
  • Synaptic transmission and plasticity remained unaffected despite these molecular changes.

Conclusions:

  • CAST/ELKS positively regulate presynaptic growth and suppress AZ expansion and CaV 2 channel levels during development.
  • CAST/ELKS are involved in regulating presynaptic morphology and CaV 2 channel subtypes.
  • Developmental compensation mechanisms preserve synaptic transmission in the absence of CAST/ELKS.