Homeostatic scaling of active zone scaffolds maintains global synaptic strength
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Homeostatic scaling of active zone scaffolds maintains global synaptic strength. / Goel, Pragya; Dufour Bergeron, Dominique; Böhme, Mathias A; Nunnelly, Luke; Lehmann, Martin; Buser, Christopher; Walter, Alexander M; Sigrist, Stephan J; Dickman, Dion.
In: The Journal of Cell Biology, Vol. 218, No. 5, 2019, p. 1706-1724.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Homeostatic scaling of active zone scaffolds maintains global synaptic strength
AU - Goel, Pragya
AU - Dufour Bergeron, Dominique
AU - Böhme, Mathias A
AU - Nunnelly, Luke
AU - Lehmann, Martin
AU - Buser, Christopher
AU - Walter, Alexander M
AU - Sigrist, Stephan J
AU - Dickman, Dion
N1 - © 2019 Goel et al.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
KW - Animals
KW - Axonal Transport
KW - Drosophila Proteins/genetics
KW - Drosophila melanogaster/physiology
KW - Homeostasis
KW - Mutation
KW - Neuromuscular Junction/physiology
KW - Synapses/physiology
KW - Synaptic Transmission/physiology
KW - rab3 GTP-Binding Proteins/genetics
U2 - 10.1083/jcb.201807165
DO - 10.1083/jcb.201807165
M3 - Journal article
C2 - 30914419
VL - 218
SP - 1706
EP - 1724
JO - Journal of Cell Biology
JF - Journal of Cell Biology
SN - 0021-9525
IS - 5
ER -
ID: 334033510