# Netrin Glycosylation Influences Chemotaxis and Haptotaxis

> **NIH NIH R21** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2024 · $233,250

## Abstract

PROJECT SUMMARY
Fidelity in directional motility is critical for development. This proposal addresses an outstanding question that
remains a major impasse in the field of developmental neurobiology: How does a single extracellular morphogen,
the secreted glycoprotein netrin-1, function as both a both a long-range diffusive cue vs a local, adhesive cue,
and both an attractive cue and a repulsive cue. Netrin-1 is critical in development of many organ systems and
branching morphogenesis from invertebrates to humans, where it promotes both attractive and repulsive motility.
However, whether netrin-1 functions as a soluble, chemotactic cue and/or as an adhesive, haptotactic cue
remains under debate. This is significant, as chemotactic cues can guide over long distances, whereas
haptotactic cues guide locally, and thus they achieve appropriate development via fundamentally distinct means.
We recently established protocols to separate and purify two distinctly glycosylated forms of netrin-1; we found
that one of these forms functions as an attractive haptotactic cue; the other acts as a chemotactic guidance cue
that elicits concentration-dependent attractive or repulsive responses. Here we will molecularly characterize
these different forms of netrin-1 with glycoanalytics. We will examine how differentially glycosylated forms of
netrin-1 evoke diverse responses during haptotaxis and chemotaxis, with the ultimate goal of developing novel
mouse models to manipulation netrin glycosylation and thus solubility in vivo. We use biochemical assays and
develop a novel tension sensor in the netrin receptor DCC to investigate how different presentations of netrin-1
alter signal transduction and mechanotransduction, respectively.

## Key facts

- **NIH application ID:** 10828904
- **Project number:** 5R21NS132364-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Stephanie Gupton
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $233,250
- **Award type:** 5
- **Project period:** 2023-04-15 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10828904

## Citation

> US National Institutes of Health, RePORTER application 10828904, Netrin Glycosylation Influences Chemotaxis and Haptotaxis (5R21NS132364-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10828904. Licensed CC0.

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