Homeostatic Scaling of Active Zone Scaffolds Maintains Global Synaptic Strength

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2019 Mar 28

PMID 30914419

Citations 42

Authors

Pragya Goel

Dominique Dufour Bergeron

Mathias A Bohme

Luke Nunnelly

Martin Lehmann

Christopher Buser

Alexander M Walter

Stephan J Sigrist

Dion Dickman

Affiliations

Soon will be listed here.

Abstract

Synaptic terminals grow and retract throughout life, yet synaptic strength is maintained within stable physiological ranges. To study this process, we investigated () mutants. Although active zone (AZ) number is doubled in mutants, a compensatory reduction in their size homeostatically adjusts global neurotransmitter output to maintain synaptic strength. We find an inverse adaptation in mutants. Additional analyses using confocal, STED, and electron microscopy reveal a stoichiometric tuning of AZ scaffolds and nanoarchitecture. Axonal transport of synaptic cargo via the lysosomal kinesin adapter Arl8 regulates AZ abundance to modulate global synaptic output and sustain the homeostatic potentiation of neurotransmission. Finally, we find that this AZ scaling can interface with two independent homeostats, depression and potentiation, to remodel AZ structure and function, demonstrating a robust balancing of separate homeostatic adaptations. Thus, AZs are pliable substrates with elastic and modular nanostructures that can be dynamically sculpted to stabilize and tune both local and global synaptic strength.

Citing Articles

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