# Characterization of mammalian COG complex-interacting Golgi trafficking machinery

> **NIH NIH R01** · UNIV OF ARKANSAS FOR MED SCIS · 2024 · $19,396

## Abstract

PROJECT SUMMARY/ABSTRACT
Intracellular membrane trafficking mediates the intracellular delivery of proteins and lipids. The process is
bidirectional and consists of the anterograde (secretory) and retrograde (endocytic) branches. Intracellular
membrane trafficking is evolutionary conserved, and its machinery is modular, with functionally homologous
components operating on different trafficking steps. Therefore, a detailed understanding of one trafficking step
will help in understanding the entire intracellular membrane trafficking process.
The Conserved Oligomeric Golgi (COG) complex operates as a vesicular tether for intra-Golgi trafficking. The
Golgi is the central hub for protein posttranslational modifications, mostly glycosylation. Consequently, the
primary job of the COG is to tether vesicles that recycle resident enzymes and cargo receptors. To achieve its
function, the COG interacts with SNAREs, Rabs, and other tethers, but the detailed understanding of these
interactions is an enigma that we propose to solve by pairwise probing of COG/partner interactions, their
kinetics, and by defining their molecular environment through proximity-labeling studies. Depletion of COG
causes accumulation of specific transport intermediates – COG complex dependent (CCD) vesicles that are
likely to represent a major class of Golgi vesicles that recycle Golgi enzymes and cargo receptors.
Mutations in COG subunits result in congenital disorders of glycosylation (CDG) type II category, which belong
to a group of autosomal recessive multi-systemic disorders with several distinguishable symptoms that include
global developmental defects and microcephaly. These deficits are often accompanied by neurological and
liver impairment. COG-CDG defects are studied in patients’ fibroblasts, which do not represent the most
affected tissues; a more flexible cell base model will benefit our progress in developing a cure for this disorder.
We hypothesize that a revealing of the molecular basis of COG/partner interactions will help in deciphering the
mechanisms of assembly/disassembly of vesicle docking platforms and that a detailed analysis of different
populations of CCD vesicles will uncover their specific origin, budding and tethering machinery and a complete
set of proteins that traffic in a COG-dependent manner. The development of cell-based models for COG-CDGs
will allow us to test the effects of different COG mutations without the need for patient involvement and pave
the way for the development of treatment protocols. To test this hypothesis, first, we will characterize in
molecular interactions between COG and its key partner proteins (Aim1). Next, we will use a degrone-assisted
COG depletion to accumulate, purify and characterize CCD vesicles (Aim2). Finally, we will develop and
characterize a novel iPSC-based cellular model for COG CDGs (Aim 3).
Success in accomplishing these aims will provide a mechanistic understanding of COG complex function,
characterize COG-de...

## Key facts

- **NIH application ID:** 11094175
- **Project number:** 3R01GM083144-15S1
- **Recipient organization:** UNIV OF ARKANSAS FOR MED SCIS
- **Principal Investigator:** VLADIMIR V LUPASHIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $19,396
- **Award type:** 3
- **Project period:** 2008-08-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11094175

## Citation

> US National Institutes of Health, RePORTER application 11094175, Characterization of mammalian COG complex-interacting Golgi trafficking machinery (3R01GM083144-15S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/11094175. Licensed CC0.

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