Disrupted WNT signaling in mouse embryonic stem cells in the absence of calreticulin

Related Experiment Video

Updated: May 4, 2026

Modeling Paracrine Noncanonical Wnt Signaling In Vitro
11:14

Modeling Paracrine Noncanonical Wnt Signaling In Vitro

Published on: December 10, 2021

1.3K

Jody Groenendyk1, Marek Michalak

  • 1Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada, T6G 2S7.

Stem Cell Reviews and Reports
|January 14, 2014
PubMed

Insights

Calreticulin deficiency disrupts WNT signaling and cell cycle progression by affecting endoplasmic reticulum calcium homeostasis. This impacts embryonic stem cell pluripotency and differentiation.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Endoplasmic reticulum (ER) homeostasis and protein quality control are crucial for cellular function.
  • The precise role of ER regulation in WNT signaling pathways remains largely uncharacterized.
  • Calreticulin's function in ER calcium buffering suggests potential involvement in signaling cascades.

Purpose of the Study:

  • To investigate the role of calreticulin in the regulation of WNT signaling.
  • To elucidate the mechanisms by which calreticulin influences cell cycle progression and pluripotency.
  • To determine the impact of ER calcium homeostasis on WNT pathway activity.

Main Methods:

  • Utilized calreticulin-deficient cell models.
  • Assessed WNT signaling pathway activation and downstream targets.
  • Analyzed cell cycle progression and pluripotency markers in embryonic stem cells.
  • Investigated the role of calreticulin's calcium-buffering capacity.

Main Results:

  • Calreticulin deficiency significantly disrupted WNT signaling and prevented cell cycle progression via the miR-302 microRNA family.
  • These effects were dependent on calreticulin's calcium-buffering capacity, impacting ER calcium release and kinase/phosphatase cascades (c-Src, Akt, PTP1B).
  • Calreticulin influences WNT3a secretion and ER retention, affecting downstream signaling and the maintenance of naive embryonic stem cell state and pluripotency transition.

Conclusions:

  • Calreticulin plays a critical, previously unrecognized role in regulating canonical WNT signaling.
  • ER calcium homeostasis and signaling are integral to WNT pathway function and embryonic stem cell fate.
  • These findings reveal novel mechanisms linking ER protein quality control to developmental signaling pathways.

More Related Videos

A Protocol for Multiple Gene Knockout in Mouse Small Intestinal Organoids Using a CRISPR-concatemer11:53

A Protocol for Multiple Gene Knockout in Mouse Small Intestinal Organoids Using a CRISPR-concatemer

Published on: July 12, 2017

20.5K
The Power of Simplicity: Sea Urchin Embryos as in Vivo Developmental Models for Studying Complex Cell-to-cell Signaling Network Interactions07:34

The Power of Simplicity: Sea Urchin Embryos as in Vivo Developmental Models for Studying Complex Cell-to-cell Signaling Network Interactions

Published on: February 16, 2017

7.5K

Related Concept Videos

Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

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...
6.4K
Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

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...
8.6K
Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

1.9K
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
1.8K
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal01:22

Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal

Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
1.8K