# NERVE-MUSCLE SYNAPSE-ORGANIZING MOLECULES

> **NIH NIH R01** · WORCESTER FOUNDATION FOR BIOMEDICAL RES · 1994 · $299,502

## Abstract

Cell-cell communication is fundamental to the function of the nervous
system.  Operations ranging from the simplest reflex arc to the most
complex processes of learning and memory rely on the accurate and
efficient exchange of information between cells.  The preeminent locus
of this exchange is the synapse.  The overall goal of the work proposed
here is to understand the molecular mechanisms that underlie synapse
formation.  The experiments will focus on agrin, a protein associated
with the synaptic basal lamina that is likely to direct the spatial
organization of acetylcholine receptors (AChRs) and other postsynaptic
components during the formation and regeneration of the neuromuscular
junction.  An essential step towards understanding agrin's mechanism of
action is to identify and characterize the agrin cell surface receptor.
In preliminary studies, methods have been developed to visualize and to
quantify the binding of exogenously added agrin to both cultured chick
myotubes and to AChR-rich membrane fractions from Torpedo electric
organ.  The putative agrin receptor defined by these methods-co-
aggregates with the AChR during agrin-induced AChR clustering on
cultured chick myotubes.  Putative agrin receptors form Torpedo
electoplax, which have agrin binding characteristics similar to those on
chick cells, have been solubilized and enriched over 200-fold as
compared to crude starting membranes.

In the work proposed here, both cell biological and biochemical
approaches will be used to further characterize and to identify the
putative agrin receptor.  The divalent cation, ionic strength, and PH
requirements and optima for agrin binding will be determined.  The cell
surface binding domain of agrin will be determined using fragments of
native and recombinant agrin.  The mechanism of the redistribution of
the putative agrin receptor, and its role in AChR clustering, will be
investigated using both pharmacological tools and treatments that
selectively inhibit AChR expression.  Biochemical, affinity
chromatography, and monoclonal antibody approaches will be used to
identify and to biochemically characterize the putative agrin receptor.
Reconstitution and immunological approaches will be used to functionally
characterize the putative agrin receptor on muscle cells.

The results of these experiments will provide fundamental insights into
synapse formation, modification, loss, and recovery.  Knowledge of these
basic mechanisms is crucial to the development of rational diagnostic
and therapeutic approaches for promoting the regeneration and
restoration of function in neural tissue damaged by trauma or disease.

## Key facts

- **NIH application ID:** 2199017
- **Project number:** 5R01HD023924-06
- **Recipient organization:** WORCESTER FOUNDATION FOR BIOMEDICAL RES
- **Principal Investigator:** JUSTIN R. FALLON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $299,502
- **Award type:** 5
- **Project period:** 1988-08-01 → 1996-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2199017

## Citation

> US National Institutes of Health, RePORTER application 2199017, NERVE-MUSCLE SYNAPSE-ORGANIZING MOLECULES (5R01HD023924-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2199017. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*