# Mechanisms of Local Protein Synthesis in Axon Arborization

> **NIH NIH R01** · UNIVERSITY OF NEVADA RENO · 2021 · $335,157

## Abstract

Local protein synthesis enables distinct biological functions of subcellular compartments.
Neuronal axons are far apart from the cell body. Although thousands of mRNAs are present in
axons and dysfunctional axonal protein synthesis is linked to multiple disorders, our
understanding of the molecular mechanisms underlying the local protein synthesis in axons is
largely limited. Axon arborization plays a critical role in nervous system function because it defines
a territory for proper synaptic connection. The long-term goal is to elucidate the mechanisms that
govern localized protein synthesis and their role in axon arborization. The objective of current
application is to gain mechanistic insights on the role and the regulation of the cytoplasmic
polyadenylation element binding protein (CPEB) in axonal protein synthesis and axon arborization
by using Drosophila as a model system. CPEB controls target protein translation through
cytoplasmic de- and poly-adenylation. Our preliminary studies support a model that a Drosophila
CPEB, Orb2 suppresses the protein synthesis of Down syndrome cell adhesion molecule
(Dscam) in the cell body through cytoplasmic deadenylation and mediates Dscam mRNA
transport to axon where Wallenda/Dual leucine zipper kinase (Wnd/DLK) de-represses the
translational suppression by Orb2. The newly developed innovative approach will be used to study
the following two aims. In Aim 1, the role of Orb2 in axonal Dscam protein synthesis will be
determined. In Aim 2, the regulatory mechanism of Orb2 by Wnd will be studied. The physiological
role of identified mechanisms will be determined using axon arborization in vivo. Orb2/CPEB is
important for long-term memory formation. Dscam is implicated in multiple brain disorders.
Wnd/DLK plays a key role in multiple neuronal events. Therefore, the contribution will be
significant because it will provide a novel role of Orb2/CPEB in axonal protein synthesis, a novel
axonal protein synthesis regulation by Wnd/DLK, and a mechanism of Dscam expression and
localization in axons. The expected outcome is the novel molecular regulatory mechanisms in
axonal protein synthesis and their role in axon arborization. Understanding the molecular
mechanisms of axonal protein synthesis and arborization will ultimately help developing effective
treatment to brain disorders.

## Key facts

- **NIH application ID:** 10104551
- **Project number:** 5R01NS116463-02
- **Recipient organization:** UNIVERSITY OF NEVADA RENO
- **Principal Investigator:** Jung Hwan Kim
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $335,157
- **Award type:** 5
- **Project period:** 2020-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10104551

## Citation

> US National Institutes of Health, RePORTER application 10104551, Mechanisms of Local Protein Synthesis in Axon Arborization (5R01NS116463-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10104551. Licensed CC0.

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