# Adherens junction proteins in neuron-glia interactions

> **NIH NIH R01** · BOSTON CHILDREN'S HOSPITAL · 2022 · $387,188

## Abstract

ABSTRACT
Intercellular interactions between neurons and glia impact diverse neurological diseases,
from autism and schizophrenia to amyotrophic lateral sclerosis (ALS) and Alzheimer's disease,
as well as responses to stroke and traumatic brain injury. Some of the most important
interactions occur at synapses, where the dendritic spines that receive information are attached
to astrocytic glia. The molecular mechanisms that assemble these cell-cell attachments remain
elusive, owing to the challenges associated with the complexity of the mammalian brain.
The goal of this study is to overcome these challenges using an innovative model of dendrite-
glia interaction in C. elegans. As described below, the central hypothesis is that dendrite-glia
contacts are mediated by proteins from adherens junctions (AJs) in epithelia. Thus, this
study lies at the intersection of two fields: applying knowledge of AJs from epithelial biology to a
long-standing question in glial biology and, conversely, leveraging the diversity of glial biology to
investigate how AJ proteins can be deployed in cellular contexts outside epithelia.
In preliminary data, innovative approaches enabled analysis of a novel class of dendrite-glia
contact. Two neurons, URX and BAG, extend dendrites to the nose where they intimately wrap
a single defined glial cell, the lateral ILso glia. Genetic screens identified factors (SAX-7, GRDN-
1, MAGI-1) that act in glia to anchor these dendrites at the nose during embryonic elongation.
When these factors are disrupted, developing dendrites detach from the nose and fail to fully
extend. SAX-7/L1CAM is a conserved neuron-glia adhesion molecule, GRDN-1 is a conserved
cytoskeletal adaptor, and MAGI-1 is a conserved scaffolding protein. Each of these proteins is
associated with AJs in epithelia; glial-specific depletion of the core AJ protein cadherin (HMR-1)
also causes the same defects, leading to the idea that AJs mediate dendrite-glia attachments.
The Aims of this study are to (Aim 1) determine the role of AJs in dendrite-glia interaction using
localization and cell-specific depletion experiments; (Aim 2) define the molecular roles of SAX-
7, GRDN-1, and MAGI-1 using in vivo rescue and in vitro binding assays; and (Aim 3) identify
additional players in this novel junction using genetic screens, focusing initially on a MAP kinase
and a formin-related protein as new players. The longer-term goal is to study these proteins in
a mouse glia model, thus translating genetic discoveries from C. elegans to mammalian brain.

## Key facts

- **NIH application ID:** 10424394
- **Project number:** 5R01NS112343-04
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Maxwell Heiman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $387,188
- **Award type:** 5
- **Project period:** 2019-07-15 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10424394

## Citation

> US National Institutes of Health, RePORTER application 10424394, Adherens junction proteins in neuron-glia interactions (5R01NS112343-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10424394. Licensed CC0.

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