# Organization and function of the periactive zone

> **NIH NIH R01** · BRANDEIS UNIVERSITY · 2020 · $380,033

## Abstract

PROJECT SUMMARY
The goal of this proposal is to understand the spatial and functional organization of the presynaptic periactive
zone (PAZ), which is found adjacent to sites of synaptic vesicle release. The PAZ is a micron-scale structure,
occupied by dozens of proteins that work together in multivalent assemblies to couple membrane remodeling
to force-generating actin polymerization. Studies of PAZ proteins in many systems have suggested that these
proteins act at multiple steps of the synaptic vesicle cycle as well as in other synaptic membrane functions
(e.g. synaptic morphogenesis and receptor traffic). It remains unknown how the micron-scale organization and
regulation of PAZ proteins direct their membrane and cytoskeleton remodeling activities to these different
neuron-specific functions. We will use the Drosophila larval neuromuscular junction (NMJ), a powerful model
synapse, to decipher how PAZ protein assemblies, activities, and cellular functions are linked. Using high-
resolution imaging, we recently found that PAZ proteins occupy both overlapping and distinct domains within
the PAZ, and that proper segregation of PAZ proteins between these domains depends on their multivalent
interactions with each other. We have also recently described PAZ-dependent dynamic actin filament
structures, which represent a direct readout of PAZ protein activities in these different domains. Using these
tools, we will ask how synapses regulate PAZ protein activities and interactions in space and time, and how
PAZ organization underlies its diverse neuron-specific functions, in response to synaptic activity and
transmission. In Aim 1, we will determine how PAZ proteins are organized at resting and active synapses using
complementary fixed, live, and super-resolution imaging methods, and develop new quantitative methods to
describe their geometric relationships in PAZ domains. In Aim 2, we will test the hypothesis that synaptic actin
patches represent clathrin-dependent synaptic vesicle recycling events, and identify the determinants of
synaptic actin patch assembly and dynamics. In Aim 3, we will ask how PAZ organization and synaptic activity
control diverse cell biological PAZ functions, including release site clearance and organization of cell adhesion
complexes. Overall, our experiments will explain how organization of the PAZ into distinct subdomains
underlies multiple functional and structural properties of synapses. PAZ proteins are implicated in multiple
neurological disorders, so deciphering their in vivo functions will be critical for understanding the etiology of
these human diseases.

## Key facts

- **NIH application ID:** 9942680
- **Project number:** 1R01NS116375-01
- **Recipient organization:** BRANDEIS UNIVERSITY
- **Principal Investigator:** Avital Adah Rodal
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $380,033
- **Award type:** 1
- **Project period:** 2020-04-15 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9942680

## Citation

> US National Institutes of Health, RePORTER application 9942680, Organization and function of the periactive zone (1R01NS116375-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9942680. Licensed CC0.

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