Homeostatic scaling of active zone scaffolds maintains global synaptic strength
Research output: Contribution to journal › Journal article › Research › peer-review
Synaptic terminals grow and retract throughout life, yet synaptic strength is maintained within stable physiological ranges. To study this process, we investigated Drosophila endophilin (endo) mutants. Although active zone (AZ) number is doubled in endo mutants, a compensatory reduction in their size homeostatically adjusts global neurotransmitter output to maintain synaptic strength. We find an inverse adaptation in rab3 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.
Original language | English |
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Journal | The Journal of Cell Biology |
Volume | 218 |
Issue number | 5 |
Pages (from-to) | 1706-1724 |
Number of pages | 19 |
ISSN | 0021-9525 |
DOIs | |
Publication status | Published - 2019 |
Externally published | Yes |
Bibliographical note
© 2019 Goel et al.
- Animals, Axonal Transport, Drosophila Proteins/genetics, Drosophila melanogaster/physiology, Homeostasis, Mutation, Neuromuscular Junction/physiology, Synapses/physiology, Synaptic Transmission/physiology, rab3 GTP-Binding Proteins/genetics
Research areas
ID: 334033510