Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
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...
Mechanism of Filopodia Formation01:39

Mechanism of Filopodia Formation

Filopodia are thin, actin-rich cellular protrusions that play an important role in many fundamental cellular functions. They vary in their occurrence, length, and positioning in different cell types, suggesting their diverse roles.
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
Tail-anchoring of Proteins in the ER Membrane01:45

Tail-anchoring of Proteins in the ER Membrane

Tail-anchored, or TA, proteins are estimated to make up to 3-5% of membrane proteins found in the eukaryotic cell. Such proteins have a single transmembrane domain located approximately 30 amino acid residues upstream from the C-terminal end. As a result, the signal recognition particle (SRP) cannot guide a TA protein to the ER membrane for cotranslational insertion. Hence, they are integrated into the ER membrane post-translationally using their C-terminal end as the anchor. TA proteins...
IP3/DAG Signaling Pathway01:11

IP3/DAG Signaling Pathway

Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and produces two-second...
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Giredestrant immobilizes the estrogen receptor to exert potent antitumor efficacy against ER-active breast cancers.

Cell chemical biology·2026
Same author

Loss of luminal lineage drives resistance to next-generation ERα antagonists in pretreated ER<sup>+</sup> HER2<sup>-</sup> locally-advanced or metastatic breast cancer.

Nature communications·2026
Same author

Preclinical models of breast cancer metastasis: strengths, limitations, and clinical relevance.

NPJ breast cancer·2026
Same author

VEL-dependent polymerization maintains the chromatin association of Polycomb proteins for the switch to epigenetic silencing.

Molecular cell·2025
Same author

Epiregulon: Single-cell transcription factor activity inference to predict drug response and drivers of cell states.

Nature communications·2025
Same author

Wnt signalosome assembly is governed by conformational flexibility of Axin and by the AP2 clathrin adaptor.

Nature communications·2025

Related Experiment Video

Updated: Jun 13, 2026

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells
10:27

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells

Published on: March 9, 2012

Stability elements in the LRP6 cytoplasmic tail confer efficient signalling upon DIX-dependent polymerization.

Ciara Metcalfe1, Carolina Mendoza-Topaz, Juliusz Mieszczanek

  • 1MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK.

Journal of Cell Science
|April 15, 2010
PubMed
Summary

Dishevelled signals through LRP5/6 co-receptors, forming signalosomes essential for Wnt/beta-catenin pathway activation. Stable polymerization of these signalosomes, driven by Dishevelled and LRP6 cytoplasmic tail elements, is crucial for their function.

More Related Videos

Using Scaffold Liposomes to Reconstitute Lipid-proximal Protein-protein Interactions In Vitro
08:53

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

Published on: January 11, 2017

Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development
09:32

Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development

Published on: June 15, 2017

Related Experiment Videos

Last Updated: Jun 13, 2026

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells
10:27

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells

Published on: March 9, 2012

Using Scaffold Liposomes to Reconstitute Lipid-proximal Protein-protein Interactions In Vitro
08:53

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

Published on: January 11, 2017

Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development
09:32

Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development

Published on: June 15, 2017

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Developmental Biology

Background:

  • Wnt/beta-catenin signaling is vital for development, tissue maintenance, and cancer.
  • Wnt binding to Frizzled receptors initiates a cascade involving Dishevelled and LRP5/6 co-receptors.
  • Phosphorylation of the LRP6 cytoplasmic tail inhibits GSK3beta, leading to beta-catenin accumulation.

Purpose of the Study:

  • To investigate the mechanism of Dishevelled-mediated signaling through LRP5/6.
  • To define the functional elements within the LRP6 cytoplasmic tail involved in signalosome formation and activity.
  • To elucidate the role of polymerization in Dishevelled-dependent signalosome function.

Main Methods:

  • Revisiting epistasis experiments to confirm Dishevelled-LRP5/6 signaling in human cells and Drosophila.
  • Constructing a fusion protein of the Dishevelled DIX domain and the LRP6 cytoplasmic tail.
  • Analyzing the phosphorylation and activity of signalosomes, focusing on polymerization and stability elements.

Main Results:

  • Dishevelled signaling occurs via LRP5/6 in human cells and Drosophila embryos.
  • A Dishevelled DIX domain fused to the LRP6 cytoplasmic tail forms potent signaling signalosomes.
  • Signalosome activity and phosphorylation depend on DIX-mediated polymerization and LRP6 cytoplasmic tail stability elements, including T1479.

Conclusions:

  • Stable polymerization is a fundamental principle governing Dishevelled-dependent signalosome function.
  • The LRP6 cytoplasmic tail contains critical stability elements that regulate signalosome activity.
  • Understanding these mechanisms provides insight into Wnt pathway regulation in various biological contexts.