# Coupled axonal protein synthesis and lipidation in axon growth and homeostasis

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2022 · $432,843

## Abstract

Axons continuously respond to external signals in their environment as they grow and
navigate toward their target tissues during development, and for maintenance and repair
in adult life. mRNA localization and local protein synthesis is a conserved mechanism that
allows for rapid and axon-autonomous responses to external trophic and guidance cues.
Despite growing appreciation for the functions of axonal protein synthesis, a major gap in
our knowledge is in understanding how the nascent proteins are further processed and
localized in axons to generate fully functional proteins. Our preliminary results suggest
that a neurotrophic factor (Nerve Growth Factor) acutely regulates local protein synthesis
and lipidation (prenylation) of newly-made proteins in axons. It has been assumed that
protein prenylation is a constitutive mechanism that occurs throughout the cytoplasm and
is permissive for cellular functions. In striking contrast, we find that, in neurons, prenylation
is under exquisite spatio-temporal control by extrinsic signals. The goal of this application
is to define whether coupled axonal protein synthesis and prenylation serves as a
regulatory mechanism to localize and enrich proteins in axonal compartments to ensure
dynamic and spatial responses to extrinsic growth-promoting cues. We will use a
combination of imaging, biochemical, and functional analyses in compartmentalized
neuronal cultures, as well as in vivo analyses in mice to accomplish this goal. These
studies will advance the knowledge of spatial modes of signaling in neurons that underlie
axon development, maintenance, and regeneration.

## Key facts

- **NIH application ID:** 10318573
- **Project number:** 5R01NS114478-03
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Rejji Kuruvilla
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $432,843
- **Award type:** 5
- **Project period:** 2019-12-01 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10318573

## Citation

> US National Institutes of Health, RePORTER application 10318573, Coupled axonal protein synthesis and lipidation in axon growth and homeostasis (5R01NS114478-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10318573. Licensed CC0.

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