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Cell-matrix's Response to Mechanical Forces01:13

Cell-matrix's Response to Mechanical Forces

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In animal cells, the extracellular matrix allows cells within tissues to withstand external stresses and transmits signals from the outside of the cell to the inside. The extracellular matrix is extensive, and its composition varies between different types of tissues. For example, the reticular fibers and ground substance make up the ECM in loose connective tissue, while collagen and bone minerals make up the ECM of bone tissue. 
Anchoring junctions mechanically attach a cell to the...
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Anchoring junctions are multiprotein complexes that help cells connect to other cells and the extracellular matrix. Anchoring junctions are present on the lateral and basal surfaces of cells, providing strong and flexible connections. Focal adhesions are often formed due to cell interactions with the ECM substrata, which initiate signal transduction via kinase cascades and other mechanisms. Together, they provide stability and tissue integrity. There are three types of anchoring junctions:...
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Adherens Junctions01:24

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Strong contact points between adjacent cells anchor them to each other, forming tissues. Such anchoring junctions are of two types –  adherens junctions and desmosomes. Adherens junctions are abundant in tissues such as  epithelium and endothelium, forming a continuous zone of adhesion called the adhesion belt. In other tissues, such as  heart muscle, they appear as clusters, linking the cells to produce coordinated heart muscle contraction.
Adherens Junctions are Dynamic
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Overview of Cell-Matrix Interactions01:24

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The extracellular matrix or ECM holds cells together to form a tissue and allows the cells within the tissue to communicate. ECM comprises proteins such as fibronectin, collagen, laminin, etc. The most abundant protein in this space is collagen. Collagen fibers are interwoven with carbohydrate-containing protein molecules called proteoglycans. ECM allows cell migration and provides a structural scaffold at cell adhesion that anchors the cell when the extracellular matrix proteins interact with...
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Gap Junctions01:37

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Multicellular organisms employ a variety of ways for cells to communicate with each other. Gap junctions are specialized proteins that form pores between neighboring cells in animals, connecting the cytoplasm between the two, and allowing for the exchange of molecules and ions. They are found in a wide range of invertebrate and vertebrate species, mediate numerous functions including cell differentiation and development, and are associated with numerous human diseases, including cardiac and...
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Tension Response at Adherens Junctions01:26

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The adherens junctions that anchor cells together are multi-protein complexes that dynamically adapt to mechanical stimuli such as tensile forces and shear stress. Mechanosensory proteins in these junctions can sense such mechanical stimuli and undergo a shift in their conformation, resulting in an altered function — a process called mechanotransduction.
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  11. Endothelial-adipocyte Cx43 Mediated Gap Junctions Can Regulate Adiposity.

Endothelial-adipocyte Cx43 Mediated Gap Junctions Can Regulate Adiposity.

Melissa A Luse1,2, Luke S Dunaway1, Shruthi Nyshadham1

  • 1Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, 22903, VA, USA.

Function (Oxford, England)
|July 10, 2024

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Perturbing Endothelial Biomechanics via Connexin 43 Structural Disruption
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View abstract on PubMed

Summary
This summary is machine-generated.

Connexin 43 (Cx43) gap junctions in adipose endothelial cells regulate fat storage and lipid metabolism. Disrupting Cx43 function worsens obesity and dyslipidemia, highlighting its role in metabolic health.

Area of Science:

  • Metabolic research
  • Cell biology
  • Cardiovascular science

Background:

  • Obesity is a metabolic disorder linked to endothelial dysfunction and cardiovascular risk.
  • Adipose capillary endothelial cells (CaECs) are vital for lipid transport and storage.
  • Understanding CaEC-adipocyte interactions is key to metabolic regulation.

Purpose of the Study:

  • Investigate CaEC-adipocyte interaction mechanisms and their metabolic impact.
  • Identify molecular players in intercellular communication within adipose tissue.
  • Determine the role of connexin 43 (Cx43) in adipose tissue function and obesity.

Main Methods:

  • Single-cell RNA sequencing (scRNAseq) to analyze CaEC gene expression.
  • Transmission electron microscopy (TEM) to visualize CaEC-adipocyte contact.
Keywords:
adiposeadipositycapillariesheterocellular contact

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  • In vitro co-culture models to study intercellular signaling.
  • Genetic manipulation of Cx43 in mice (knockout and phosphorylation-resistant mutants).

    • Main Results:

    • scRNAseq revealed enhanced fatty acid handling in CaECs from high-fat diet (HFD) mice.
    • In vitro co-culture showed lipid-induced upregulation of fatty acid binding protein 4.
    • Endothelial Cx43 deletion exacerbated HFD-induced adiposity and dyslipidemia.
    • Phosphorylation of Cx43 (Ser368) increased with HFD and lipid treatment, suggesting gap junction closure.
    • Cx43S368A mutant mice showed reduced adiposity and improved lipid profiles on HFD.

    Conclusions:

    • Adipose capillary endothelial cells possess specialized lipid handling capabilities.
    • Intercellular communication, potentially via Cx43, is crucial for adipose tissue function.
    • Cx43-mediated gap junction communication regulates adiposity and lipid metabolism, offering a potential therapeutic target for obesity.
    metabolism
    obesity