# Downregulation of Rab3D:  Critical Role in Golgi Disorganization and the Pathogenesis of Alcoholic Liver Disease

> **NIH VA I01** · OMAHA VA  MEDICAL CENTER · 2021 · —

## Abstract

The goal of this VA Merit is to examine how ethanol exposure results in impaired function of the Golgi apparatus.
The Golgi apparatus (also called the Golgi body or Golgi complex) packages proteins into membrane bound
vesicles inside the cell before the vesicles are sent to their destination. As such, this organelle resides at the
intersection of the secretory, lysosomal, and endocytic pathways; it is known to be of particular importance in
processing proteins for secretion. Previous work from our laboratory has identified multiple defects in
endocytosis, protein trafficking, and secretion, after alcohol administration, but we have not until now, examined
a role for altered Golgi function in these processes. Because the incidence of alcoholic liver disease (ALD) is
greater in the Veteran population and more than half of all medical admissions in VA Medical Centers across the
country are linked to alcohol abuse, we are focusing efforts towards the identification of potential targets to
intervene during the progressive injury which occurs after chronic alcohol administration, and perhaps the Golgi
will prove to be such a target. Of central importance to our study is the role of a small GTPase, Rab3D, which
is involved in exocytosis, secretion and vesicle trafficking. We have shown that Rab3D protein content was
significantly decreased after alcohol administration, and recently we have obtained exciting new preliminary data
that ethanol-impaired Rab3D function plays an important role in Golgi disorganization and fragmentation. The
studies proposed in this application will extend our ongoing investigation of how ethanol alters hepatocyte
biology, specifically in protein processing, to an examination of its role in transport through the Golgi. We provide
a concept as to how alcohol-induced remodeling of Golgi morphology is a significant impairment of post-Golgi
trafficking, and this leads to utilization of trans-Golgi membranes for the formation of autophagosomes. These
recent and novel findings provide an excellent foundation for this proposal and support our central hypothesis
that EtOH-induced down-regulation of Rab3D disrupts the assembly and function of Golgi apparatus leading to
impaired protein trafficking and metabolism, contributing to liver injury. To examine this hypothesis, we have
proposed three specific aims; in Aim 1 we will determine how the function of Rab3D regulates the integrity of the
Golgi, in Aim 2 we will examine how autophagy is linked to EtOH-induced Golgi disorganization, and in Aim 3
we will explore recent preliminary data examining recovery of compact Golgi and reconstitution of trans-Golgi
membranes. Altogether, successful completion of these aims will characterize the effect of EtOH on Golgi
disorganization, and establish a role for altered Rab3D during this process. We will be able to correlate
mechanisms of alcohol-mediated liver cell trafficking impairments with impaired Golgi function and provide key
information that...

## Key facts

- **NIH application ID:** 10115517
- **Project number:** 5I01BX004171-02
- **Recipient organization:** OMAHA VA  MEDICAL CENTER
- **Principal Investigator:** Carol A. Casey
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2020-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10115517

## Citation

> US National Institutes of Health, RePORTER application 10115517, Downregulation of Rab3D:  Critical Role in Golgi Disorganization and the Pathogenesis of Alcoholic Liver Disease (5I01BX004171-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10115517. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*