Related Experiment Video

Updated: Oct 18, 2025

Molecular Modulation by Lentivirus-Delivered Specific shRNAs in Endoplasmic Reticulum Stressed Neurons
10:50

Molecular Modulation by Lentivirus-Delivered Specific shRNAs in Endoplasmic Reticulum Stressed Neurons

Published on: April 24, 2021

1.2K

Mannan-binding lectin deficiency augments hepatic endoplasmic reticulum stress through IP3R-controlled calcium

Yu Chen1, Mengyao Hu2, Fan Deng3

  • 1Department of Medical Laboratory, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, Guangdong 510515, China; Guangdong Province Key Laboratory of Proteomics, Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, China.

Cell Calcium
|September 30, 2021
PubMed

Insights

Mannan-binding lectin (MBL) deficiency worsens liver injury by disrupting calcium homeostasis and endoplasmic reticulum (ER) stress responses. MBL normally protects against ER stress-induced liver damage.

Area of Science:

  • Immunology
  • Cellular Biology
  • Hepatology

Background:

  • Aberrant endoplasmic reticulum (ER) calcium release disrupts calcium homeostasis, leading to ER stress and liver damage.
  • Mannan-binding lectin (MBL), a calcium-dependent innate immune protein synthesized by hepatocytes, is crucial for recognizing pathogens.
  • MBL deficiency is common and linked to increased susceptibility to liver diseases.

Purpose of the Study:

  • To investigate the role of MBL in ER stress-induced liver injury.
  • To elucidate the mechanisms by which MBL influences ER calcium homeostasis and stress pathways.

Main Methods:

  • Genetic MBL ablation in mice.
  • Analysis of ER stress markers and calcium signaling pathways.
  • Investigation of MBL interaction with ER-resident proteins.

Main Results:

  • Mice lacking MBL showed increased sensitivity to ER stress-induced liver injury.
  • MBL deficiency accelerated the dissociation of PKR-like ER kinase (PERK) from immunoglobulin heavy chain binding protein (BiP).
  • MBL deficiency enhanced the PERK-C/EBP-homologous protein (CHOP) pathway and promoted inositol 1,4,5-trisphosphate receptor (IP3R)-mediated calcium release, worsening liver injury.

Conclusions:

  • MBL plays a protective role in maintaining ER calcium homeostasis and mitigating ER stress.
  • MBL deficiency exacerbates liver injury through impaired ER calcium regulation and heightened ER stress.
  • These findings offer new insights into liver damage associated with ER stress in MBL-deficient individuals.
Keywords:
CalciumEndoplasmic reticulum stressInositol 1,4,5-trisphosphate receptorLiver injuryMannan-binding lectin

More Related Videos

Live Cell Calcium Imaging Combined with siRNA Mediated Gene Silencing Identifies Ca2+ Leak Channels in the ER Membrane and their Regulatory Mechanisms13:40

Live Cell Calcium Imaging Combined with siRNA Mediated Gene Silencing Identifies Ca2+ Leak Channels in the ER Membrane and their Regulatory Mechanisms

Published on: July 7, 2011

18.3K
Direct Imaging of ER Calcium with Targeted-Esterase Induced Dye Loading TED09:32

Direct Imaging of ER Calcium with Targeted-Esterase Induced Dye Loading TED

Published on: May 7, 2013

19.3K

Related Concept Videos

Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.7K
IP3/DAG Signaling Pathway01:11

IP3/DAG Signaling Pathway

Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
12.8K
The Unfolded Protein Response01:37

The Unfolded Protein Response

The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
5.4K
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...
6.1K
Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
5.4K
Export of Misfolded Proteins out of the ER01:32

Export of Misfolded Proteins out of the ER

After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
4.2K