Authors
Kelsey J Clements, Leslie C Griffith
Published in
eNeuro. Aug 31, 2026. Epub Aug 31, 2026.
Abstract
Activity-dependent structural plasticity is essential for the growth and remodeling of synaptic connections. At the Drosophila melanogaster larval neuromuscular junction (NMJ), spaced stimulation induces the translation-dependent formation of ghost boutons (GBs), which are immature boutons that lack a corresponding postsynaptic structure. Calcium/calmodulin-dependent protein kinase II (CaMKII) has previously been implicated in GB formation and is locally translated at synapses, raising the possibility that activity-dependent CaMKII synthesis contributes to GB formation. We examined activity-induced synaptic outgrowth in female larvae using a spaced depolarization paradigm combined with genetic manipulations of the endogenous CaMKII locus. While whole-animal CaMKII null mutants exhibited fewer GBs after spaced depolarization, selective disruption of activity-dependent CaMKII synthesis by deletion of the CaMKII 3' untranslated region (3'UTR) in either presynaptic motor neurons or postsynaptic muscle cells had no effect on GB formation. Consistent with this, inhibition of the signaling pathways upstream of CaMKII synthesis also did not impair bouton outgrowth. Cell-specific deletion of the CaMKII coding region in presynaptic neurons also did not alter GB formation, but postsynaptic deletion significantly reduced it. These findings demonstrate that local synthesis of CaMKII is dispensable for activity-dependent ghost bouton formation. Instead, our results indicate that only steady-state CaMKII protein is necessary for this specific type of structural plasticity and identifies a new trans-synaptic function for postsynaptic CaMKII in GB formation. These findings distinguish the role of CaMKII protein from CaMKII synthesis and suggest that other locally translated proteins underlie the protein synthesis dependence of GB formation.Significance Statement Local protein synthesis is thought to support long-lasting forms of synaptic plasticity. At the Drosophila neuromuscular junction, CaMKII is synthesized during patterned stimulation, which also triggers CaMKII-dependent ghost bouton formation, suggesting CaMKII local synthesis might be involved in this form of structural plasticity. In contrast to this hypothesis, disrupting activity-dependent CaMKII translation in either presynaptic or postsynaptic cells had no effect on ghost bouton formation. Instead, loss of CaMKII protein in the whole animal blocked synaptic outgrowth, and loss of postsynaptic CaMKII protein reduced it. Our findings indicate that CaMKII protein function, but not local CaMKII synthesis, is involved in activity-dependent ghost bouton formation. Identifying the precise molecular players driving local translation-dependent remodeling remains a task for future research.
PMID:
42674867
Bibliographic data and abstract were imported from PubMed on 01 Sep 2026.
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