Rapid homeostatic modulation of transsynaptic nanocolumn rings

Proc Natl Acad Sci U S A. 2022 Nov 8;119(45):e2119044119. doi: 10.1073/pnas.2119044119. Epub 2022 Nov 2.


Robust neural information transfer relies on a delicate molecular nano-architecture of chemical synapses. Neurotransmitter release is controlled by a specific arrangement of proteins within presynaptic active zones. How the specific presynaptic molecular architecture relates to postsynaptic organization and how synaptic nano-architecture is transsynaptically regulated to enable stable synaptic transmission remain enigmatic. Using time-gated stimulated emission-depletion microscopy at the Drosophila neuromuscular junction, we found that presynaptic nanorings formed by the active-zone scaffold Bruchpilot (Brp) align with postsynaptic glutamate receptor (GluR) rings. Individual rings harbor approximately four transsynaptically aligned Brp-GluR nanocolumns. Similar nanocolumn rings are formed by the presynaptic protein Unc13A and GluRs. Intriguingly, acute GluR impairment triggers transsynaptic nanocolumn formation on the minute timescale during homeostatic plasticity. We reveal distinct phases of structural transsynaptic homeostatic plasticity, with postsynaptic GluR reorganization preceding presynaptic Brp modulation. Finally, homeostatic control of transsynaptic nano-architecture and neurotransmitter release requires the auxiliary GluR subunit Neto. Thus, transsynaptic nanocolumn rings provide a substrate for rapid homeostatic stabilization of synaptic efficacy.

Keywords: Drosophila; active zone; glutamate receptor; homeostatic plasticity; synaptic nano-architecture.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drosophila / metabolism
  • Drosophila Proteins* / metabolism
  • Membrane Proteins / metabolism
  • Neuromuscular Junction* / metabolism
  • Neurotransmitter Agents / metabolism
  • Receptors, Glutamate / metabolism
  • Synapses / metabolism
  • Synaptic Transmission


  • Receptors, Glutamate
  • Drosophila Proteins
  • Neurotransmitter Agents
  • Neto protein, Drosophila
  • Membrane Proteins