Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Specialized roles for cysteine cathepsins in health and disease
Jochen Reiser, … , Brian Adair, Thomas Reinheckel
Jochen Reiser, … , Brian Adair, Thomas Reinheckel
Published October 1, 2010
Citation Information: J Clin Invest. 2010;120(10):3421-3431. https://doi.org/10.1172/JCI42918.
View: Text | PDF
Science in Medicine Article has an altmetric score of 6

Specialized roles for cysteine cathepsins in health and disease

  • Text
  • PDF
Abstract

Cathepsins were originally identified as proteases that act in the lysosome. Recent work has uncovered nontraditional roles for cathepsins in the extracellular space as well as in the cytosol and nucleus. There is strong evidence that subspecialized and compartmentalized cathepsins participate in many physiologic and pathophysiologic cellular processes, in which they can act as both digestive and regulatory proteases. In this review, we discuss the transcriptional and translational control of cathepsin expression, the regulation of intracellular sorting of cathepsins, and the structural basis of cathepsin activation and inhibition. In particular, we highlight the emerging roles of various cathepsin forms in disease, particularly those of the cardiac and renal systems.

Authors

Jochen Reiser, Brian Adair, Thomas Reinheckel

×

Figure 4

Cytosolic cathepsin L and its function in proteinuric kidney disease.

Options: View larger image (or click on image) Download as PowerPoint
Cytosolic cathepsin L and its function in proteinuric kidney disease.
Ph...
Phosphorylation of synaptopodin by PKA or CaMKII promotes 14-3-3 binding, which protects synaptopodin and dynamin against cathepsin L–mediated cleavage, thereby contributing to a stationary podocyte phenotype and an intact glomerular filtration barrier. Dephosphorylation of synaptopodin by calcineurin abrogates the interaction with 14-3-3. This renders the cathepsin L cleavage sites of synaptopodin accessible and promotes the degradation of synaptopodin and dynamin, thereby promoting a motile phenotype and the development of proteinuria. The calcineurin inhibitor CsA and the cathepsin inhibitor E64 safeguard against proteinuria by stabilizing synaptopodin and dynamin protein levels in podocytes.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Referenced in 5 patents
297 readers on Mendeley
See more details