NF2/Merlin mediates contact-dependent inhibition of EGFR mobility and internalization via cortical actomyosin

Related Experiment Video

Updated: Mar 31, 2026

Labeling F-actin Barbed Ends with Rhodamine-actin in Permeabilized Neuronal Growth Cones
09:14

Labeling F-actin Barbed Ends with Rhodamine-actin in Permeabilized Neuronal Growth Cones

Published on: March 17, 2011

15.2K

Christine Chiasson-MacKenzie1, Zachary S Morris1, Quentin Baca2

  • 1Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA 02129 Department of Pathology, Massachusetts General Hospital, Charlestown, MA 02129 Department of Pathology, Harvard Medical School, Boston, MA 02115.

The Journal of Cell Biology
|October 21, 2015
PubMed

Insights

Normal cells stop dividing at confluence due to contact-dependent inhibition of proliferation. The study reveals the neurofibromatosis type 2 (NF2) tumor suppressor Merlin and Ezrin regulate this process by controlling epidermal growth factor receptor (EGFR) signaling.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Contact-dependent inhibition of proliferation normally prevents cells from overgrowing.
  • The molecular mechanisms underlying this crucial cellular process remain largely unknown.
  • The neurofibromatosis type 2 (NF2) tumor suppressor Merlin was previously implicated in this phenomenon.

Purpose of the Study:

  • To elucidate the molecular basis of contact-dependent inhibition of proliferation.
  • To investigate the role of Merlin and related proteins in regulating cell growth.
  • To understand how cell-cell contact influences epidermal growth factor receptor (EGFR) signaling.

Main Methods:

  • Investigated the function of Merlin and Ezrin in cell proliferation assays.
  • Examined the localization and activity of EGFR in response to cell contact.
  • Utilized biochemical and imaging techniques to study the cortical cytoskeleton and mechanical force transduction.

Main Results:

  • Merlin inhibits epidermal growth factor receptor (EGFR) internalization and signaling upon cell-cell contact.
  • Localization of Merlin to the cortical cytoskeleton is essential for contact-dependent EGFR regulation.
  • Merlin and Ezrin function together to transmit mechanical forces, controlling EGFR mobility and activity.

Conclusions:

  • Merlin and Ezrin are key components in a signaling pathway linking cell-cell contact to the inhibition of mitogenic signaling.
  • Mechanical forces at cell junctions are transduced via the actomyosin cytoskeleton to regulate EGFR.
  • This provides new insights into how cells control proliferation in response to their environment.

More Related Videos

Author Spotlight: Optogenetic Inhibition of Rho1-Mediated Actomyosin Contractility Coupled with Measurement of Epithelial Tension in Drosophila Embryos12:35

Author Spotlight: Optogenetic Inhibition of Rho1-Mediated Actomyosin Contractility Coupled with Measurement of Epithelial Tension in Drosophila Embryos

Published on: April 14, 2023

2.0K
Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans08:12

Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans

Published on: October 5, 2020

3.4K

Related Concept Videos

Cell Motility through Blebbing01:16

Cell Motility through Blebbing

Blebs are a type of membrane protrusion formed by the internal hydrostatic pressure of the cytoplasm. Blebs are observed in several cell types, including fibroblasts, immune cells, and single-celled organisms like the amoeba. The primary function of blebs is cell locomotion and apoptosis, but they are also found during necrosis and cell division. The life cycle of a bleb comprises an initiation phase followed by the expansion and retraction phases.
Blebbing Through the Matrix
In multicellular...
2.7K
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...
4.4K
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
3.0K
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...
3.8K
Fibronectins Connect Cells with ECM01:25

Fibronectins Connect Cells with ECM

Fibronectin is an adhesive glycoprotein present in the extracellular matrix of embryogenic and adult tissue. These molecules primarily aid in regulating cell motility and attachment. A fibronectin molecule is composed of two identical polypeptide chains attached to each other by a pair of disulfide bonds at the C-terminal.
Both proteoglycans and collagen are attached to fibronectin proteins, which, in turn, are attached to integrin proteins. These integrin proteins interact with transmembrane...
3.7K
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...
3.4K