Related Experiment Video

Updated: Apr 25, 2026

Author Spotlight: Developing Parmodulins to Target Protease-Activated Receptors for Inflammation Control
07:13

Author Spotlight: Developing Parmodulins to Target Protease-Activated Receptors for Inflammation Control

Published on: May 24, 2024

1.1K

Obligatory role for endothelial heparan sulphate proteoglycans and caveolae internalization in catestatin-dependent

Sara Fornero1, Eleonora Bassino1, Roberta Ramella1

  • 1Department of Life Sciences and Systems Biology, University of Turin, Via Accademia Albertina 13, 10123 Turin, Italy.

Biomed Research International
|August 20, 2014
PubMed

Insights

Catestatin peptide interacts with heparan sulphate proteoglycans, triggering caveolae-dependent endocytosis. This process is essential for catestatin

Area of Science:

  • Endothelial cell biology
  • Molecular mechanisms of peptide signaling
  • Cardiovascular research

Background:

  • Catestatin, a peptide derived from chromogranin-A, influences cardiovascular functions, immunity, inflammation, and metabolism.
  • Previous research indicated catestatin's cardiac antiadrenergic effect involves PI3K-dependent nitric oxide (NO) release from endothelial cells.
  • The specific receptor mediating this action remained unidentified.

Purpose of the Study:

  • To investigate the interaction of catestatin with membrane heparan sulphate proteoglycans.
  • To determine if this interaction leads to caveolae-dependent endocytosis.
  • To elucidate the role of proteoglycans and caveolae in catestatin-mediated endothelial nitric oxide synthase (eNOS) activation.

Main Methods:

  • Experiments conducted on bovine aortic endothelial cells.
  • Confocal microscopy utilized to quantify endocytotic vesicle trafficking.
  • Fluorimetric measurements in live cells assessed catestatin colocalization with heparan sulphate proteoglycans and caveolin-1 internalization.
  • Immunofluorescence and immunoblot analysis evaluated catestatin-dependent eNOS activation.

Main Results:

  • Catestatin (5 nM) demonstrated colocalization with heparan sulphate proteoglycans.
  • A significant increase in caveolae-dependent endocytosis and caveolin-1 internalization was observed, reduced by heparinase and wortmannin.
  • Catestatin failed to induce Ser(1179) eNOS phosphorylation after heparinase and methyl-β-cyclodextrin treatments.

Conclusions:

  • Heparan sulphate proteoglycans are crucial for catestatin binding to endothelial cells.
  • Caveolae-dependent endocytosis is an obligatory pathway for catestatin signaling.
  • Proteoglycan interaction and caveolae internalization are essential for catestatin-mediated eNOS activation in endothelial cells.

More Related Videos

Demonstration of Proteolytic Activation of the Epithelial Sodium Channel ENaC by Combining Current Measurements with Detection of Cleavage Fragments08:56

Demonstration of Proteolytic Activation of the Epithelial Sodium Channel ENaC by Combining Current Measurements with Detection of Cleavage Fragments

Published on: July 5, 2014

12.8K
Targeting Cysteine Thiols for in Vitro Site-specific Glycosylation of Recombinant Proteins11:25

Targeting Cysteine Thiols for in Vitro Site-specific Glycosylation of Recombinant Proteins

Published on: October 4, 2017

6.0K

Related Concept Videos

Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.9K
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
4.4K
Catenins01:23

Catenins

Catenins are characterized by multiple binding domains and dynamic structures that allow them to function as linker proteins in cell junction complexes. All catenins, except α-catenin, contain a characteristic protein sequence called the armadillo repeat and are therefore also called armadillo proteins.
Catenins in Cell Junctions
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the...
2.2K
Receptor-mediated Endocytosis01:38

Receptor-mediated Endocytosis

Overview
105.3K
Receptor-mediated Endocytosis01:20

Receptor-mediated Endocytosis

Receptor-mediated endocytosis is when bulk amounts of specific molecules are imported into a cell after binding to cell surface receptors. The molecules bound to these receptors are taken into the cell through inward folding of the cell surface membrane, which is eventually pinched off into a vesicle within the cell. Structural proteins, such as clathrin, coat the budding vesicle.
Clathrin-Mediated Endocytosis of LDL
One well-characterized example of receptor-mediated endocytosis is the...
10.2K
Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
4.7K