Related Experiment Video

Updated: Jun 25, 2025

Analysis of SCAP N-glycosylation and Trafficking in Human Cells
11:27

Analysis of SCAP N-glycosylation and Trafficking in Human Cells

Published on: November 8, 2016

8.7K

Dishevelled localization and function are differentially regulated by structurally distinct sterols

Sonali Sengupta1, Jazmine D W Yaeger1, Maycie M Schultz1

  • 1Cellular Therapies and Stem Cell Biology Group, Sanford Research, Sioux Falls, SD, 57104, USA.

Biorxiv : the Preprint Server for Biology
|May 27, 2024
PubMed

Insights

Intracellular sterols regulate Dishevelled (DVL) protein activity by altering its membrane association and interactions. Sterol accumulation impairs DVL2 function, highlighting the importance of sterol homeostasis in cell signaling.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Dishevelled (DVL) proteins are crucial for cell signaling pathways like Wnt/β-catenin, regulating development and disease.
  • DVL proteins associate with the plasma membrane via cholesterol binding, but the specifics of this interaction and its consequences are not fully understood.

Purpose of the Study:

  • To investigate the structural requirements and cellular impacts of Dishevelled (DVL)-sterol association.
  • To determine how intracellular sterol accumulation affects DVL activity and signaling.

Main Methods:

  • In silico and molecular analyses of DVL-sterol binding.
  • Assessment of DVL2 plasma membrane association and nuclear localization in response to sterol changes.
  • Evaluation of DVL2 protein-protein interactions under altered sterol conditions.

Main Results:

  • Intracellular sterol accumulation leads to aberrant DVL activity.
  • Sterol orientation within the DVL-PDZ domain influences DVL-sterol binding.
  • Accumulated sterols impair DVL2 membrane association, promoting its nuclear localization via Foxk2.
  • Altered intracellular sterols selectively disrupt DVL2 protein-protein interactions.

Conclusions:

  • Sterol specificity is a key regulator of DVL signaling.
  • Intracellular sterols exert distinct effects on DVL activity.
  • Maintaining intracellular sterol homeostasis is critical for proper cell signaling.
Keywords:
DishevelledWntcholesterol biosynthesissterols

More Related Videos

Metabolic Labeling and Membrane Fractionation for Comparative Proteomic Analysis of Arabidopsis thaliana Suspension Cell Cultures11:44

Metabolic Labeling and Membrane Fractionation for Comparative Proteomic Analysis of Arabidopsis thaliana Suspension Cell Cultures

Published on: September 28, 2013

14.1K
Fluorescence-Based Measurements of Phosphatidylserine/Phosphatidylinositol 4-Phosphate Exchange Between Membranes08:49

Fluorescence-Based Measurements of Phosphatidylserine/Phosphatidylinositol 4-Phosphate Exchange Between Membranes

Published on: March 14, 2021

4.0K

Related Concept Videos

Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.4K
Membrane Domains01:18

Membrane Domains

The membrane domains concentrate specific lipids and proteins at one place within the membrane, which helps in cell signaling, adhesion, and other critical cellular processes. These domains can differ in size, composition, function, and lifespan.
Protein Domains
The membrane comprises a group of distinct proteins responsible for carrying out a cell's specific function. For example, the plasma membrane of the human sperm, or a single germ cell, contains a unique set of proteins in the...
5.4K
What are Lipids?01:31

What are Lipids?

Lipids function as structural components of cellular membranes, in addition to acting as energy reservoirs and signaling molecules. They are thus crucial to all living organisms.  The three biologically important classes of lipids are triglycerides, phospholipids, and steroids.
Non-Polar and Hydrophobic Characteristics of Lipids
Lipids are a structurally and functionally diverse group of hydrocarbons—compounds consisting of carbon and hydrogen atoms. The carbon-carbon and...
7.5K
Mechanisms of Membrane Domain Formation00:59

Mechanisms of Membrane Domain Formation

Different physical properties of lipids and proteins allow them to localize and form distinct islands or domains in the membrane. Some membrane domains are formed due to protein-protein interactions, whereas others are formed due to the presence of specific lipids such as sphingolipids and sterols—for example, large proteins, such as bacteriorhodopsin, aggregate and create distinct domains.
Another mechanism for membrane domain formation involves membrane proteins interacting with...
3.0K
Cholesterol: Significance and Regulation01:29

Cholesterol: Significance and Regulation

Although not a source of energy, cholesterol plays a significant role as a foundational structure for bile salts, steroid hormones, and vitamin D, as well as being a crucial component of plasma membranes. Approximately 15% of blood cholesterol is derived from our diet, with the remainder synthesized from acetyl CoA by the liver and intestines. Cholesterol is eliminated from the body through its conversion into bile salts, which are eventually discarded in the feces.
Considering cholesterol and...
538
Asymmetric Lipid Bilayer01:35

Asymmetric Lipid Bilayer

Biological membranes show uneven distribution of different types of lipids in the inner and outer layers, resulting in transverse asymmetric membranes. The treatment of the erythrocyte membrane with the enzyme phospholipase confirmed the asymmetric nature of the lipid bilayer. The enzyme hydrolyzes lipids into fatty acids and hydrophilic groups. The phospholipase acts only on the outer layer of the membrane, while the inner layer remains intact. The phospholipase treatment resulted in 80%...
7.2K