# Control of neural circuit assembly by cell surface protein interactions

> **NIH NIH R01** · CALIFORNIA INSTITUTE OF TECHNOLOGY · 2022 · $566,624

## Abstract

Project Summary/Abstract
In both invertebrate and vertebrate nervous systems, cell recognition molecules control assembly of synaptic
circuits during development. We discovered a network of interacting cell surface proteins (CSPs) through an in
vitro binding (“interactome”) screen for interactions among all Drosophila immunoglobulin superfamily (IgSF)
proteins. In this network, 11 DIP proteins in one IgSF subfamily interact with 21 Dpr proteins in another
subfamily, with affinities ranging from 1 µM to 200 µM. Each DIP and Dpr is expressed by a unique subset of
neurons in each area of the developing brain. The connectome of the Drosophila pupal optic lobe (OL) is
assembled by activity-independent mechanisms. DIP::Dpr interactions are important for OL and neuromuscular
system wiring, and loss of individual DIPs or Dprs can alter synaptic connectivity and cause neuronal death. In
this proposal, we address the functions of affinity variation and avidity by examining how changes in DIP::Dpr
binding affinity and expression level affect synaptic terminal development in the neuromuscular system and
synaptic connectivity in the OL. We also examine other interaction networks that may be involved in
determination of the optic lobe connectome. Two such networks are the Beat/Side network of 22 IgSF proteins,
which we also discovered in the interactome screen, and a network of ligands for receptor tyrosine
phosphatases (RPTPs), which are neuronal signaling receptors that regulate axon guidance and
synaptogenesis. We will examine how these three networks work together in vivo to control synaptic
connectivity between specific lamina and medulla neurons in the OL. We will generate a comprehensive map
of interactions and measure binding affinities for all of the Beat/Side proteins using surface plasmon resonance.
To validate interactions in the RPTP network and identify inter-network interactions, we will develop a method
for multiplexed interactome screening using high-avidity 60-mer nanoparticles that may be able to identify
lower-affinity interactions missed in earlier screens. The objectives of the present application are to define how
the affinities of DIP::Dpr interactions affect synaptic connection patterns, to examine how DIPs and Dprs work
together with other families of cell recognition molecules, and to develop improved methods to detect and
characterize in vitro interactions among CSPs. We plan to attain these objectives through three Specific Aims.
Aim 1: Define the functions of DIP::Dpr affinity variation in control of muscle innervation. Aim 2: Examine the
roles of DIP::Dpr affinity and of interplay among cell adhesion and signaling molecules in determination of
synaptic connectivity in the OL. Aim 3: Map in vitro interactions among Beats, Sides, RPTPs, and other CSPs.
The expected outcome of the proposed research will be the acquisition of new insights into the mechanisms by
which interactions among cell recognition molecules control the assembly ...

## Key facts

- **NIH application ID:** 10443123
- **Project number:** 2R01NS028182-32A1
- **Recipient organization:** CALIFORNIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Engin Ozkan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $566,624
- **Award type:** 2
- **Project period:** 1990-01-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10443123

## Citation

> US National Institutes of Health, RePORTER application 10443123, Control of neural circuit assembly by cell surface protein interactions (2R01NS028182-32A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10443123. Licensed CC0.

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