Related Experiment Video

Updated: Feb 25, 2026

Determining Membrane Protein Topology Using Fluorescence Protease Protection FPP
08:14

Determining Membrane Protein Topology Using Fluorescence Protease Protection FPP

Published on: April 20, 2015

18.4K

Membrane Targeting of Disheveled Can Bypass the Need for Arrow/LRP5

Prameet Kaur1, Vanessa Yuk Man Lam1, Anirudh Gautam Mannava2

  • 1Yale-NUS College, National University of Singapore, Block MD6, Centre for Translational Medicine, Yong Loo Lin School of Medicine, 14 Medical Drive, Level 10 South, 10-02M, Singapore, 117599, Singapore.

Scientific Reports
|August 2, 2017
PubMed

Insights

Membrane-tethering Disheveled (Dsh) protein activates Wnt signaling without co-receptors. Specific Dsh domains are dispensable for this membrane-initiated canonical Wnt pathway signaling.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The Wnt signaling pathway is crucial for cell proliferation and differentiation.
  • Disheveled (Dsh/Dvl) acts as a signal transducer in both canonical and non-canonical Wnt pathways.
  • Dsh's role as a switch between Wnt signaling branches is complex and not fully understood.

Purpose of the Study:

  • To investigate the membrane-proximal events in Wnt signaling activation.
  • To determine if Dsh recruitment to the membrane is sufficient for canonical Wnt signaling.
  • To identify the specific protein domains of Dsh involved in membrane-initiated signaling.

Main Methods:

  • Constructing membrane-tethered Dsh proteins.
  • Assessing canonical Wnt signaling activation in the presence and absence of Wnt co-receptors.
  • Mapping the functional domains (DEP and PDZ) of membrane-tethered Dsh.

Main Results:

  • Membrane-tethering of Dsh is sufficient to activate canonical Wnt signaling, even without the Arrow/LRP5/6 co-receptor.
  • The DEP and PDZ domains of Dsh are dispensable for canonical signaling when Dsh is membrane-tethered.
  • These domains remain essential for signaling in untethered, endogenous Dsh.

Conclusions:

  • A model is proposed where Arrow/LRP5/6 localizes Dsh to the membrane to initiate canonical Wnt signaling.
  • Dsh functions downstream of Arrow in the canonical Wnt signaling pathway.
  • Membrane recruitment is a critical step for Dsh-mediated canonical Wnt signal activation.

More Related Videos

Method to Visualize and Analyze Membrane Interacting Proteins by Transmission Electron Microscopy10:49

Method to Visualize and Analyze Membrane Interacting Proteins by Transmission Electron Microscopy

Published on: March 5, 2017

14.0K
Using Scaffold Liposomes to Reconstitute Lipid-proximal Protein-protein Interactions In Vitro08:53

Using Scaffold Liposomes to Reconstitute Lipid-proximal Protein-protein Interactions In Vitro

Published on: January 11, 2017

9.4K

Related Concept Videos

Directing Proteins to the Rough Endoplasmic Reticulum01:34

Directing Proteins to the Rough Endoplasmic Reticulum

The organelle-specific signaling sequences direct proteins synthesized in the cytosol to their final destination like ER, mitochondria, peroxisomes, etc. Some of the proteins directed to ER are then trafficked via vesicles to other organelles within the cell or the extracellular environment through the Golgi complex. For example, the rough ER synthesizes soluble proteins for transportation to the lysosomes or secretion out of the cell. It can also synthesize transmembrane proteins that can...
18.1K
Mechanism of Lamellipodia Formation01:31

Mechanism of Lamellipodia Formation

Cells migrating in response to external stimuli form lamellipodia, which are thin membrane protrusions supported by a mesh of linked, branched, or unbranched actin filaments. These actin filaments interact with myosin motor proteins, creating the dynamic actomyosin complex within the cytoskeleton. Contractility, or the ability to generate contractile stress, is inherent to the actomyosin complex. It helps cells detect the stiffness of the surrounding ECM and exert contractile force for...
3.8K
Rab Proteins01:14

Rab Proteins

Rab proteins constitute the largest family of monomeric GTPases, of which 70 members are present in humans. Rab proteins and their effectors regulate consecutive stages of vesicle transport such as vesicle transport, docking, and fusion to the correct recipient membrane.
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
5.3K
Export of Misfolded Proteins out of the ER01:32

Export of Misfolded Proteins out of the ER

After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
5.3K
Pinching-off of Coated Vesicles01:32

Pinching-off of Coated Vesicles

Vesicle budding is orchestrated by distinct cytosolic proteins such as adaptor proteins, coat proteins, and GTPases. To initiate vesicle budding, membrane-bending proteins containing crescent-shaped BAR domains bind to the lipid heads in the bilayer and distort the membrane to form a protein-coated vesicle bud. Adaptors proteins such as AP2 for clathrin-coated vesicles can nucleate on the deformed membrane. Finally, coat proteins such as clathrin or COPI and COPII assemble into a coat forming...
4.3K
Membrane Asymmetry Regulating Transporters01:19

Membrane Asymmetry Regulating Transporters

Enzymes like flippase, floppase, and scramblase transfer phospholipids from one layer to another in the membrane, thereby affecting membrane asymmetry.
Flippase
Eukaryotic flippases are type-IV P-type ATPases or P4-ATPases belonging to P-type ATPase family proteins that are membrane-bound pumps involved in the ATP-mediated transport of ions and molecules across the membrane. Flippases flip specific phospholipids from the outer to the inner leaflet of a membrane. All P4-ATPases have one...
7.6K