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 Experiment Videos

Requirements for estrogen receptor alpha membrane localization and function.

Albert J Evinger1, Ellis R Levin

  • 1Department of Biological Chemistry, University of California Irvine School of Medicine, Irvine, CA 92717, USA.

Steroids
|May 3, 2005
PubMed
Summary
This summary is machine-generated.

Related Concept Videos

You might also read

Related Articles

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

Sort by
Same author

Both Nuclear and Membrane Estrogen Receptor Alpha Impact the Expression of Estrogen Receptors and Plasticity Markers in the Mouse Hypothalamus and Hippocampus.

Biology·2023
Same author

Membrane Estrogen Receptor β Is Sufficient to Mitigate Cardiac Cell Pathology.

Endocrinology·2022
Same author

Effect of Androgen Suppression on Clinical Outcomes in Hospitalized Men With COVID-19: The HITCH Randomized Clinical Trial.

JAMA network open·2022
Same author

Membrane-Initiated Estrogen, Androgen, and Progesterone Receptor Signaling in Health and Disease.

Endocrine reviews·2021
Same author

Role of nuclear and membrane estrogen signaling pathways in the male and female reproductive tract.

Differentiation; research in biological diversity·2020
Same author

Mechanisms by Which Membrane and Nuclear ER Alpha Inhibit Adipogenesis in Cells Isolated From Female Mice.

Endocrinology·2020
Same journal

Emerging trends for therapeutic valuation of Cyclopamine: Structural features, mechanism of action, and formulation strategies.

Steroids·2026
Same journal

The antiproliferative and antimigratory properties of the 3-biotin-B-norcholesteryl benzimidazole derivative in MCF-7 cells are mediated through G1 phase arrest and apoptosis.

Steroids·2026
Same journal

Development and validation of an LC-MS method for quantification of sex steroid hormones in skeletal muscle.

Steroids·2026
Same journal

Circulating 4β-hydroxycholesterol as a biomarker of CYP3A4 activity: beyond drug development.

Steroids·2026
Same journal

Impact of glycosylation position on flavonoid isomers' inhibition of breast cancer-associated enzyme CYP1B1.

Steroids·2026
Same journal

Synthesis NMR characterization and X-ray structure of α,β-unsaturated steroid spiroketal lactones. evaluation of cytotoxicity and anti-inflammatory activity.

Steroids·2026
See all related articles

Estrogen receptor alpha (ERalpha) membrane localization requires caveolin-1 and serine 522. Estradiol (E2) binding enhances ERalpha membrane association, activating signaling pathways crucial for cell growth and survival in breast cancer.

Area of Science:

  • Cell Biology
  • Molecular Endocrinology
  • Cancer Signaling

Background:

  • Estrogen receptor alpha (ERalpha) functions at the plasma membrane, but structural requirements for its localization and function are not fully understood.
  • Previous research has begun to elucidate these requirements, highlighting the need for further investigation into ERalpha's membrane dynamics.

Purpose of the Study:

  • To investigate the structural requirements for ERalpha translocation to the plasma membrane.
  • To understand the role of caveolin-1 and specific ERalpha residues in membrane localization.
  • To elucidate the signaling pathways activated by membrane-localized ERalpha in the presence of estradiol (E2).

Main Methods:

  • Site-directed mutagenesis of ERalpha (Serine 522 to Alanine).
  • Deletion mutagenesis of caveolin-1 scaffolding domain.

Related Experiment Videos

  • Co-immunoprecipitation to assess protein-protein interactions.
  • Cellular fractionation and Western blotting to determine protein localization.
  • Analysis of downstream signaling pathway activation (Src, ERK, PI3K).

    • Main Results:

    • ERalpha translocation to the membrane in the absence of estrogen depends on caveolin-1 and Serine 522.
    • Mutation of Serine 522 to Alanine decreased ERalpha membrane localization by 62% and reduced association with caveolin-1.
    • Deletion of the caveolin-1 scaffolding domain significantly impaired ERalpha membrane localization.
    • Estradiol (E2) increased membrane localization of ERalpha, Shc, and IGF-1R.
    • Membrane ERalpha activates G-proteins, leading to Src activation and downstream signaling (ERK, PI3K) involved in cell growth and survival, particularly in breast cancer.

    Conclusions:

    • Caveolin-1 and Serine 522 are critical for ERalpha membrane localization.
    • Membrane-bound ERalpha acts as an atypical G-protein coupled receptor, initiating signaling cascades.
    • This pathway, involving Src and EGFR activation, contributes to cell growth and survival in breast cancer, offering potential therapeutic targets.