# Mechanisms in COPII-Dependent Transport

> **NIH NIH R01** · DARTMOUTH COLLEGE · 2020 · $548,391

## Abstract

Project Summary
Selective protein trafficking in the secretory pathway is vital for cell function and growth. Our research
program is focused on coat-dependent sorting mechanisms that catalyze transport between the
endoplasmic reticulum (ER) and Golgi complex. Here nascent secretory proteins are translated at the ER
and then fully folded proteins are selectively packaged into COPII coated vesicles for anterograde transport
to the Golgi complex. This forward pathway is balanced by retrograde transport from the Golgi, which
selectively returns proteins to the ER in COPI coated vesicles. To ensure delivery of only folded secretory
proteins, a process known as ER quality control retains nascent proteins in the ER until correctly folded or
ultimately targets terminally misfolded proteins for degradation. Mechanisms that coordinate efficient sorting
of cargo into transport vesicles with ER quality control are not well understood. We have identified a set of
transmembrane cargo receptors that perform important functions in coat-dependent sorting and quality
control in the early secretory pathway. This research proposal will address key questions in the field
regarding how cargo binding to receptors is controlled to achieve net directional transport of proteins and
how cargo receptors function in ER quality control. The specific aims of the proposal are to: (1) determine
how the Erv41-Erv46 cargo receptor catalyzes retrieval of escaped ER resident proteins; (2) define
molecular sorting signals in cargo that are required for Erv41-Erv46 recognition; (3) investigate how Erv41-
Erv46 retrieves misfolded proteins from post-ER compartments; and (4) determine how the Erv26 and
Erv29 anterograde cargo receptors function in ER quality control. We will rigorously test our hypotheses in a
yeast model by exploiting molecular genetics to monitor protein function in vivo, through cell free assays
with isolated ER and Golgi membranes in vitro and in reconstitution experiments with purified factors.
Defining the molecular mechanisms that underlie these fundamental cellular processes should improve
current approaches to treat human diseases connected to secretory pathway function.

## Key facts

- **NIH application ID:** 9923675
- **Project number:** 5R01GM052549-26
- **Recipient organization:** DARTMOUTH COLLEGE
- **Principal Investigator:** CHARLES K BARLOWE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $548,391
- **Award type:** 5
- **Project period:** 1995-05-01 → 2021-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9923675

## Citation

> US National Institutes of Health, RePORTER application 9923675, Mechanisms in COPII-Dependent Transport (5R01GM052549-26). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9923675. Licensed CC0.

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