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Cited by 61Cellular Mechanics and InteractionsNeurofibromatosis and Schwannoma CasesProtein Kinase Regulation and GTPase Signaling

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

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Chiasson-MacKenzie, Christine, Morris, Zachary S., Baca, Quentin, Morris, Brett, Coker, Joanna K., Mirchev, Rossen, Jensen, Anne E., Carey, Thomas +3 more·2015·Journal of Cell Biology
DOI 10.1083/jcb.201503081PMC PMC4621825
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Abstract

The proliferation of normal cells is inhibited at confluence, but the molecular basis of this phenomenon, known as contact-dependent inhibition of proliferation, is unclear. We previously identified the neurofibromatosis type 2 (NF2) tumor suppressor Merlin as a critical mediator of contact-dependent inhibition of proliferation and specifically found that Merlin inhibits the internalization of, and signaling from, the epidermal growth factor receptor (EGFR) in response to cell contact. Merlin is closely related to the membrane–cytoskeleton linking proteins Ezrin, Radixin, and Moesin, and localization of Merlin to the cortical cytoskeleton is required for contact-dependent regulation of EGFR. We show that Merlin and Ezrin are essential components of a mechanism whereby mechanical forces associated with the establishment of cell–cell junctions are transduced across the cell cortex via the cortical actomyosin cytoskeleton to control the lateral mobility and activity of EGFR, providing novel insight into how cells inhibit mitogenic signaling in response to cell contact.

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Authors
Chiasson-MacKenzie, C., Morris, Z. S., Baca, Q., Morris, B., Coker, J. K., Mirchev, R., Jensen, A. E., Carey, T., Stott, S. L., Golan, D. E., & McClatchey, A. I.
Affiliations
  • Harvard University (US)
  • Massachusetts General Hospital (US)
Corresponding author
McClatchey, Andrea I.
ORCID
Venue
Journal of Cell Biology
Publisher
Rockefeller University Press
Published
2015-10-19
Volume
211
Issue
2
Pages
391-405
ISSN
  • 0021-9525 (ISSN-L)
  • 1540-8140
DOI
10.1083/jcb.201503081
PMC
PMC4621825
OpenAlex
W1852638080
Cited by
61
References
1
Citations by year
2026: 1 · 2025: 4 · 2024: 3 · 2023: 6 · 2022: 6 · 2021: 2 · 2020: 3 · 2019: 12 · 2018: 6 · 2017: 11 · 2016: 6 · 2015: 1
FWCI
4.23
Type
journal article
Language
en
Open access
Licence
cc-by-nc-sa
Locations
  • The Journal of Cell Biology (publishedVersion, cc-by-nc-sa)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
Funders
  • National Heart, Lung, and Blood Institute (R01HL116327, R01HL032854)
  • National Cancer Institute (R01CA113733)
  • National Institute of General Medical Sciences (F31GM078720, T32GM007306)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
  • Health Sciences › Medicine › Neurology › Neurofibromatosis and Schwannoma Cases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords
Merlin, epidermal growth factor receptor, EGFR internalization, ezrin, cell-cell contact, mechanotransduction, cell cortex, mitogenic signaling, cell confluence
MeSH terms
Ezrin, Actomyosin, Animals, Cells, Cultured, Contact Inhibition, Cytoskeletal Proteins, Intercellular Junctions, Membrane Proteins, Microfilament Proteins, Actin Cytoskeleton, Stress, Mechanical, Protein Transport, Nonmuscle Myosin Type IIA, Neurofibromin 2, RNA Interference, RNA, Small Interfering, Mechanotransduction, Cellular, Cell Proliferation, Mice, ErbB Receptors

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