Related Experiment Video
Updated: May 14, 2026
19:16
The Importance of Correct Protein Concentration for Kinetics and Affinity Determination in Structure-function Analysis
Published on: March 18, 2010
Enzymatic activity of lysosomal carboxypeptidase (cathepsin) A is required for proper elastic fiber formation and
Volkan Seyrantepe1, Aleksander Hinek, Junzheng Peng
1Department of Medical Genetics, CHU Sainte Justine Research Center, University of Montreal, Montreal, Quebec, Canada.
Circulation
|April 9, 2008
Summary
Cathepsin A (CathA) deficiency leads to hypertension and reduced elastic fibers by impairing endothelin-1 inactivation and elastic fiber formation. This study reveals CathA
Area of Science:
- Biochemistry
- Genetics
- Physiology
Background:
- Lysosomal carboxypeptidase, cathepsin A (CathA), is crucial for lysosomal enzyme stability and cell surface complexes.
- Genetic defects in CathA cause galactosialidosis, a metabolic disorder with lysosomal storage.
- Phenotypic features like hypertension suggest CathA's role beyond lysosomal storage.
Purpose of the Study:
- To investigate the in vivo function of cathepsin A (CathA) beyond its lysosomal protective role.
- To elucidate CathA's involvement in hemodynamic regulation and elastic fiber formation.
Main Methods:
- Generation of a gene-targeted mouse model with catalytically inactive CathA (Ser190Ala substitution).
- Assessment of lysosomal enzyme complex formation and activity.
- Measurement of endothelin-1 degradation rates and arterial blood pressure.
- Histological analysis of elastic fiber content in various tissues.
Main Results:
- Mice with inactive CathA maintained lysosomal complexes without secondary enzyme deficiencies.
- These mice exhibited reduced endothelin-1 degradation and significantly elevated arterial blood pressure.
- A scarcity of elastic fibers was observed in the lungs, aortic adventitia, and skin of CathA-deficient mice.
Conclusions:
- Cathepsin A (CathA) functions in vivo as an endothelin-1-inactivating enzyme.
- CathA plays a critical role in the effective formation of elastic fibers.
- These findings highlight CathA's importance in both metabolic regulation and cardiovascular health.
Related Concept Videos
01:31Lysosomes
Lysosomes are membrane-enclosed spherical sacs derived from the Golgi apparatus. The most important function of the lysosome is degrading macromolecules and biological polymers that are released during membrane trafficking events such as the secretory, endocytic, autophagic, and phagocytic pathways. The degradation is carried out by several hydrolytic enzymes active in an acidic environment of the lysosomal lumen. These acid hydrolases are involved in cellular processes such as cell signaling,...
01:22Lysosomal Hydrolases
Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
01:24Caspases
Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.
01:23Role of Matrix Metalloproteases in Degradation of ECM
Matrix metalloproteases (MMPs) are enzymes involved in the hydrolysis of proteins and glycoproteins of the extracellular matrix. MMPs are essential for the migration and proliferation of cells through the dense matrix network, throughout embryonic development, and throughout morphogenesis. The first MMP activity discovered was a collagenase in a tadpole's tail undergoing metamorphosis. The active collagen deposition and modifications lead to the morphogenesis of tadpoles into the adult body.
A...
A...
01:23Catenins
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 adherens...
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 adherens...
01:17The Proteasome Structure
The ubiquitin-proteasome pathway is a well-known mechanism utilized by eukaryotic cells to remove cytoplasmic proteins that are misfolded, damaged, or no longer needed. In this pathway, the protein that needs to be eliminated undergoes a process called ubiquitination, where a chain of ubiquitin molecules is attached to the 48th lysine residue of the target protein. This ubiquitin modification helps the proteasome distinguish between a target protein and a healthy protein.
The proteasome is an...
The proteasome is an...