# Novel Regulation of Postsynaptic Assembly in Drosophila

> **NIH NIH R21** · HARVARD MEDICAL SCHOOL · 2020 · $466,125

## Abstract

ABSTRACT
 Chemical synapse assembly is an essential process underlying the development and plasticity of neural
circuits. Synaptogenesis involves a complex sequence of coordinated events requiring many components in
presynaptic and postsynaptic cells. Because these specialized junctions are organized and modified locally in
response to a range of developmental or external stimuli, synapse formation is highly regulated. Decades of
research have identified many relevant signaling pathways and factors that control the stages of synapse
development in a range of systems. In this search, invertebrate models such as the neuromuscular junctions
(NMJs) of Drosophila and C. elegans have offered sophisticated tools for identifying and dissecting mechanisms
underlying the assembly and maturation of the sites of neurotransmitter release. This proposal aims to leverage
unpublished discoveries suggesting that the Transforming Acidic Coiled-Coil (TACC) family serves to control
synaptic protein synthesis via interactions with eIF-4E and other factors. Preliminary findings suggest that
Drosophila dTACC occupies postsynaptic location that forms in response to active zone assembly and serves
to regulate synapse development. We find that dTACC physically interacts with factors associated with
translation including eIF-4E and CPEB/Orb2, and dTACC appears necessary and sufficient to control the protein
level of the postsynaptic kinase dPak that regulates assembly of glutamate receptor clusters. This fabric of data
leads us to a working model where (1) postsynaptic dTACC acts to inhibit the translation of dPak, and
possibly other factors, thus controlling the extent and/or timing of synapse maturation. Moreover, we
postulate that (2) dTACC activity is controlled by upstream trans-synaptic signaling events that
coordinate NMJ development. Our goals are to test these two central ideas in order to open a robust new line
of inquiry into mechanisms of postsynaptic translational regulation in this powerful model synapse. While our
working model draws upon classic work on the eIF-4E-Binding Protein Maskin/TACC3 during early development,
the TACC protein family has yet to be appreciated in this capacity at the neuronal synapse, thus presenting an
exciting opportunity to identify a new mechanism for this conserved family of proteins that may be relevant in
other nervous systems.

## Key facts

- **NIH application ID:** 10110177
- **Project number:** 1R21NS119932-01
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** David L. Van Vactor
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $466,125
- **Award type:** 1
- **Project period:** 2020-09-30 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10110177

## Citation

> US National Institutes of Health, RePORTER application 10110177, Novel Regulation of Postsynaptic Assembly in Drosophila (1R21NS119932-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10110177. Licensed CC0.

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