Related Experiment Video
Updated: Jan 31, 2026
08:37
Purification of the Sarco-Endoplasmic Reticulum Ca2+-ATPase from Rabbit Muscle
Published on: March 21, 2025
823
Reduced SERCA Function Preferentially Affects Wnt Signaling by Retaining E-Cadherin in the Endoplasmic Reticulum
Annabelle Suisse1, Jessica E Treisman1
1Kimmel Center for Biology and Medicine at the Skirball Institute and Department of Cell Biology, NYU School of Medicine, 540 First Avenue, New York, NY 10016, USA.
Cell Reports
|January 10, 2019
Summary
Endoplasmic reticulum calcium levels, regulated by SERCA pumps, are crucial for cell signaling. Disrupting calcium homeostasis impacts Wingless, Notch, and Hippo pathways, with complex implications for cancer therapy.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Proper calcium homeostasis in the endoplasmic reticulum (ER) is vital for protein processing and trafficking.
- Defects in protein trafficking can significantly affect cellular signaling pathways.
Purpose of the Study:
- To investigate the role of ER calcium levels, specifically those regulated by the SERCA pump, in Wingless (Wg) signaling.
- To determine the impact of altered ER calcium on other key signaling pathways like Notch and Hippo.
Main Methods:
- Utilized hypomorphic and null SERCA alleles in conjunction with the loss of the Orai calcium channel.
- Assessed the effects of varying ER calcium thresholds on Armadillo/β-catenin localization and signaling.
- Analyzed the impact on Wingless, Notch, and Hippo signaling pathways.
Main Results:
- Reduced ER calcium sequesters Armadillo/β-catenin, disrupting Wingless signaling by preventing its release from E-cadherin within the ER.
- Wingless signaling is highly sensitive to minor ER calcium reductions.
- Notch and Hippo signaling pathways are disrupted at intermediate ER calcium levels.
- Complete loss of SERCA function leads to apoptosis.
Conclusions:
- ER calcium levels precisely regulate multiple oncogenic signaling pathways (Wingless, Notch, Hippo) in a dose-dependent manner.
- The complex, differential effects on these pathways suggest that SERCA inhibitors may have complicated outcomes as cancer therapeutics.
Related Concept Videos
01:39Endoplasmic Reticulum
107.8K
The Endoplasmic Reticulum (ER) in eukaryotic cells is a substantial network of interconnected membranes with diverse functions, from calcium storage to biomolecule synthesis. A primary component of the endomembrane system, the ER manufactures phospholipids critical for membrane function throughout the cell. Additionally, the two distinct regions of the ER specialize in the manufacture of specific lipids and proteins.
107.8K
01:43The Endoplasmic Reticulum
21.4K
The endoplasmic reticulum or ER makes up for more than half of the membranes in a cell and accounts for 10% of total cell volume. It is also the primary protein and lipid synthesis factory for most cell organelles, such as the Golgi apparatus, lysosomes, secretory vesicles, and the plasma membrane. Despite being the most extensive and functionally complex subcellular organelle, ER was the last to be discovered. After years of deliberation, Keith Porter and George Palade in the year 1954,...
21.4K
01:21Smooth Endoplasmic Reticulum
8.0K
Smooth endoplasmic reticulum or smooth ER is a sub-organelle with specialized functions in animal cells and plant cells. It is often associated with the tubule morphology of the endoplasmic reticulum.
The ER provides optimal conditions for synthesizing steroid hormones and lipids, such as phospholipids and triglycerides. Traditionally, lipid metabolism was considered to be a smooth ER function. However, there is no direct evidence to prove that rough ER is completely excluded from lipid...
The ER provides optimal conditions for synthesizing steroid hormones and lipids, such as phospholipids and triglycerides. Traditionally, lipid metabolism was considered to be a smooth ER function. However, there is no direct evidence to prove that rough ER is completely excluded from lipid...
8.0K
01:34Directing Proteins to the Rough Endoplasmic Reticulum
17.6K
The organelle-specific signaling sequences direct proteins synthesized in the cytosol to their final destination like ER, mitochondria, peroxisomes, etc. Some of the proteins directed to ER are then trafficked via vesicles to other organelles within the cell or the extracellular environment through the Golgi complex. For example, the rough ER synthesizes soluble proteins for transportation to the lysosomes or secretion out of the cell. It can also synthesize transmembrane proteins that can...
17.6K
02:54Canonical Wnt Signaling Pathway
10.6K
The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
10.6K
01:41Non-Canonical Wnt Signaling Pathways
8.4K
Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
8.4K