# Regulation of epithelial junctions and lumen morphogenesis by the Scribble/SGEF/Dlg1 complex

> **NIH NIH R01** · UNIVERSITY OF TOLEDO · 2021 · $305,563

## Abstract

PROJECT SUMMARY
 Most internal organs consist of a monolayer of polarized epithelial cells surrounding a central lumen that
establish a barrier that segregate the internal medium from the outside environment. One of the key determinants
of establishment of apicobasal polarity in epithelial cells is the Scribble complex. The Scribble complex is a multi-
protein scaffolding platform which functions by recruiting other binding partners, to build spatially distinct
signaling complexes. A major barrier to understand the formation of the epithelium is our poor understanding of
the mechanisms that control the function of the Scribble complex. For over two decades, the Scribble complex
was known to function as a module from genetic studies, but it was unclear how the members of the complex
interacted with each other, and their link to the regulators of adhesion and polarity. To close this gap, my lab is
focused in defining the precise composition, mechanism of formation and regulation of the Scribble complex. We
have recently shown that SGEF, a RhoG-specific GEF, is a new component of the Scribble complex that acts
as a scaffold to form a ternary complex by interacting directly with Scribble and Dlg1, and plays a role during
junction formation, apical contractility, E-cadherin stability and lumen formation. Based on these findings, the
objective of this proposal is to define the molecular mechanisms that regulate the function of the Scribble complex
in the regulation of cell-cell junctions’ assembly and maintenance, and lumen formation. We will test the central
hypothesis that the incorporation of SGEF into the Scribble complex stimulates its catalytic activity, which in turn
activates RhoG to regulate the stability of cell-cell junctions, as well as lumen opening and number. We propose
the following specific aims to test this hypothesis. Aim 1. Define the spatiotemporal regulation of SGEF and
RhoG activity by the Scribble complex. Here we will test our working hypothesis that binding to Scribble and
Dlg1 targets and/or activates SGEF to cell-cell junctions which promote the localized activation of RhoG; Aim 2.
Determine the mechanism by which the Scribble/SGEF/Dlg1 complex regulates E-cadherin stability. Here we
will test our working hypothesis that the activation of RhoG downstream SGEF stabilizes E-cadherin at the
membrane by regulating its recycling and/or degradation; Aim 3. Determine how the Scribble/SGEF/Dlg1
complex regulates lumen opening and number. Here, we will test our working hypothesis that, the formation of
the Scribble/SGEF/Dlg1 is required the formation of cysts with a single, central open lumen in 3D cysts.
 This approach is innovative, as it provides mechanistic insight on the function of the Scribble complex.
This contribution will be significant because it will shed light on the fundamental mechanisms controlling cell-cell
adhesion and its role in the establishment of in epithelial cells and tissues. Understanding how cell adhesion ...

## Key facts

- **NIH application ID:** 10129403
- **Project number:** 5R01GM136826-02
- **Recipient organization:** UNIVERSITY OF TOLEDO
- **Principal Investigator:** Rafael Garcia-Mata
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $305,563
- **Award type:** 5
- **Project period:** 2020-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10129403

## Citation

> US National Institutes of Health, RePORTER application 10129403, Regulation of epithelial junctions and lumen morphogenesis by the Scribble/SGEF/Dlg1 complex (5R01GM136826-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10129403. Licensed CC0.

---

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