# Regulation of biosynthetic cargo transport in neurons

> **NIH NIH F31** · UNIVERSITY OF WISCONSIN-MADISON · 2021 · $34,318

## Abstract

Project Summary
 The goal of this proposal is to understand the mechanisms by which newly synthesized secretory proteins
emerge from the endoplasmic reticulum (ER) in neurons, move through the endomembrane system, and
ultimately reach the surface of axons and dendrites. Previous studies in numerous mammalian cell types have
clearly demonstrated that the coat protein complex II (COPII) machinery plays an integral role in directing most
secretory proteins from the ER to the ER-Golgi intermediate compartment (ERGIC), a vesicular-tubular cluster
of membranes directly adjacent to budding sites on the ER. Cargoes are then typically transported to the
perinuclear Golgi apparatus and subsequently delivered to their final destinations. However, comparatively little
is known about the architecture of the early secretory pathway in neurons, and even less is understood about
local protein export from the ER within axons and dendrites. Using differentiated human induced pluripotent stem
cells (iPSCs), I have developed a physiologically relevant system to study biosynthetic secretory protein transport
in glutamatergic cortical neurons. Additionally, I will leverage genome edited human iPSCs to define the impact
of a pathological variant in Trk-fused gene (TFG), which underlies an early onset form of hereditary spastic
paraplegia (HSP) that is characterized by progressive axonopathy within the corticospinal tract. My studies will
provide new insights into the importance of localized protein transport from the ER in distal portions of neurites,
while simultaneously providing me with outstanding training in stem cell biology, biochemistry, high resolution
imaging, and genetics. In preliminary studies, I have already generated a large number of tools to study
biosynthetic protein trafficking in neurons, including CRISPR/Cas9-modified iPSCs that natively express tagged
subunits of the COPII machinery and other components of the secretory pathway (using HaloTag), as well as
fluorescently-labeled cargoes that can be released upon demand from the ER. Thus, I am exceptionally well-
prepared to tackle the studies outlined in my proposal, which should help to uncover new pathomechanisms that
contribute to corticospinal axonopathy observed in patients with HSP, laying the foundation for the future
development of therapeutic approaches to ameliorate disease. Importantly, the fellowship training plan created
specifically for me will facilitate growth of my operational and technical skills in experimental design, data
acquisition, and data analysis, while simultaneously fostering development of my professional skills in science
communication, mentoring, and leadership. Overall, the intellectual environment at UW-Madison and its
infrastructure are ideal to ensure my long-term success as a productive biomedical researcher.

## Key facts

- **NIH application ID:** 10233167
- **Project number:** 1F31NS122443-01
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Iryna Pustova
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $34,318
- **Award type:** 1
- **Project period:** 2021-04-01 → 2023-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10233167

## Citation

> US National Institutes of Health, RePORTER application 10233167, Regulation of biosynthetic cargo transport in neurons (1F31NS122443-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10233167. Licensed CC0.

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