# Characterization of mammalian COG complex-interacting Golgi trafficking machinery

> **NIH NIH R01** · UNIV OF ARKANSAS FOR MED SCIS · 2024 · $409,543

## 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:** 10813202
- **Project number:** 5R01GM083144-15
- **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:** $409,543
- **Award type:** 5
- **Project period:** 2008-08-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10813202

## Citation

> US National Institutes of Health, RePORTER application 10813202, Characterization of mammalian COG complex-interacting Golgi trafficking machinery (5R01GM083144-15). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10813202. Licensed CC0.

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