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Related Concept Videos

Insertion of Single-pass Transmembrane Proteins in the RER01:26

Insertion of Single-pass Transmembrane Proteins in the RER

Integral membrane proteins are proteins adhered to the lipid bilayer of a cell organelle or membrane. They can be of two types: transmembrane integral proteins that span the lipid bilayer and monotopic proteins that are attached to either side of the membrane but do not pass through it.
Integral transmembrane proteins possess transmembrane and extra membrane domains. The transmembrane domains are primarily made of 20-25 hydrophobic amino acids arranged in a helical secondary confirmation. These...
Internal Receptors01:31

Internal Receptors

Many cellular signals are hydrophilic and therefore cannot pass through the plasma membrane. However, small or hydrophobic signaling molecules can cross the hydrophobic core of the plasma membrane and bind to internal, or intracellular, receptors that reside within the cell. Many mammalian steroid hormones use this mechanism of cell signaling, as does nitric oxide (NO) gas.
Insertion of Multi-pass Transmembrane Proteins in the RER01:29

Insertion of Multi-pass Transmembrane Proteins in the RER

The rough ER membrane synthesizes, assembles, and embeds transmembrane proteins in diverse topologies. These proteins function as transporters or channels and can remain in the ER membrane or are sent to the Golgi complex, lysosome, and cell membrane.
The multipass transmembrane proteins are the type IV integral membrane proteins with multiple topogenic sequences determining their spatial arrangement in the ER membrane. Nearly all multipass proteins lack a cleavable signal sequence and use...
Role of ER in the Secretory Pathway01:17

Role of ER in the Secretory Pathway

Eukaryotic cells have a special pathway that enables communication between various intracellular membrane-bound compartments and also with the extracellular environment. This pathway is termed as the secretory pathway.
Components of the secretory pathway
About a third of proteins synthesized in the cell are sorted via the secretory route. They shuffle between different compartments in membrane-bound vesicles until they reach their final destination. The main intracellular compartments involved...
Types of Receptors: Internal Receptors01:07

Types of Receptors: Internal Receptors

Many cellular signals are hydrophilic and cannot pass through the plasma membrane. However, small or hydrophobic signaling molecules can cross the hydrophobic core of the plasma membrane and bind intracellular receptors that reside within the cell cytoplasm or nucleus. Many mammalian steroid hormones and nitric oxide (NO) gas use this cell signaling mechanism.
Similar to membrane-bound receptors, the binding of a ligand to the intracellular receptor of causes a conformational change in the...
Transducer Mechanism: Nuclear Receptors01:31

Transducer Mechanism: Nuclear Receptors

Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:

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Related Experiment Video

Updated: May 29, 2026

Transmembrane Domain Oligomerization Propensity determined by ToxR Assay
06:45

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Published on: May 26, 2011

Splice isoform estrogen receptors as integral transmembrane proteins.

Kyung Hee Kim1, Derek Toomre, Jeffrey R Bender

  • 1Departments of Internal Medicine (Cardiovascular Medicine) and Immunobiology and the Raymond and Beverly Sackler Foundation Cardiovascular Laboratory, Yale University School of Medicine, New Haven, CT 06511, USA.

Molecular Biology of the Cell
|September 23, 2011
PubMed
Summary

Estrogen receptor ER46 acts as a type I transmembrane protein, initiating rapid cell signals. This membrane localization is crucial for endothelial nitric oxide synthase activation and nitric oxide production.

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Area of Science:

  • Molecular biology
  • Cell signaling
  • Endocrinology

Background:

  • Steroid hormone receptors modulate gene transcription and rapidly transduce kinase activation signals.
  • Estrogen receptor (ER) α has a splice isoform, ER46, that triggers membrane-initiated signals upon ligand binding.
  • ER46 activates endothelial nitric oxide synthase (eNOS), leading to endothelial nitric oxide (NO) production.

Purpose of the Study:

  • To define the topological orientation of ER46 at the plasma membrane.
  • To investigate the role of ER46's transmembrane domain in its signaling function.
  • To explore the potential of transmembrane steroid hormone receptors as therapeutic targets.

Main Methods:

  • Utilized ecliptic pHluorin-fused ER46 for live imaging.
  • Employed total internal reflection fluorescence microscopy in human endothelial cells.
  • Introduced mutations in ER46's transmembrane hydrophobic core (Isoleucine-386).

Main Results:

  • ER46 conforms to a type I transmembrane protein structure at the plasma membrane.
  • Mutation of Isoleucine-386 disrupted membrane spanning and obscured the N-terminal ectodomain.
  • Mutated ER46 showed reduced membrane-impermeant estrogen binding, diminished rapid eNOS activation, and decreased NO production.
  • Genomic induction of an estrogen response element-luciferase reporter was maintained despite mutations.

Conclusions:

  • Transmembrane pools of steroid hormone receptors, like ER46, function as efficient signaling molecules.
  • ER46's transmembrane topology is critical for its rapid, non-genomic signaling.
  • Transmembrane steroid hormone receptors represent potential novel therapeutic targets.