# Mechanisms of membrane protein trafficking and AKT/mTOR signaling that promote myelin sheath stability and growth

> **NIH NIH F31** · UNIVERSITY OF COLORADO DENVER · 2021 · $33,983

## Abstract

Project Summary
 Myelin sheaths are built through a dynamic process of axonal adhesion and membrane biogenesis to
form a compact, multilamellar structure. Interestingly, only a fraction of sheaths that initiate at the onset of
myelination will stabilize and mature to form compact myelin. We know that axonal adhesion proteins are
important for determining sheath stability. However, there is a fundamental gap in our understanding of how
these molecules are maintained at the myelin/axolemma interface during the dynamic process of myelin
wrapping. Additionally, AKT/mTOR signaling is an important driver of membrane biogenesis in
oligodendrocytes. However, we do not know whether AKT/mTOR signaling drives ensheathment events or
rather this pathway acts downstream of axonal adhesion. Therefore, our objective here is to investigate the
mechanisms for trafficking myelin/axonal adhesion molecules and for activating AKT/mTOR signaling to
promote sheath stabilization and growth. In aim 1, we will use a combination of genetic manipulations, in vivo
live-cell imaging, and biochemistry to investigate the mechanisms of membrane trafficking that localize MAG to
the axolemma interface. In aim 2 we will use a MAG knockout fish line to perform genetic epistasis
experiments to determine if the AKT/mTOR pathway promotes sheath stabilization downstream of axonal
adhesion. Together this project will elucidate how AKT/mTOR signaling interfaces with membrane protein
trafficking pathways to build a myelin sheath.

## Key facts

- **NIH application ID:** 10328875
- **Project number:** 5F31NS118830-02
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Adam R Almeida
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $33,983
- **Award type:** 5
- **Project period:** 2020-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10328875

## Citation

> US National Institutes of Health, RePORTER application 10328875, Mechanisms of membrane protein trafficking and AKT/mTOR signaling that promote myelin sheath stability and growth (5F31NS118830-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10328875. Licensed CC0.

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