Chapter

Cellular Peptidases in Immune Functions and Diseases 2

Volume 477 of the series Advances in Experimental Medicine and Biology pp 305-315

Ceramide as an Activator Lipid of Cathepsin D

  • Michael HeinrichAffiliated withInstitute of Immunology, University of Kiel
  • , Marc WickelAffiliated withInstitute of Immunology, University of Kiel
  • , Supandi Winoto-MorbachAffiliated withInstitute of Immunology, University of Kiel
  • , Wulf Schneider-BrachertAffiliated withInstitute of Immunology, University of Kiel
  • , Thomas WeberAffiliated withInstitute of Immunology, University of KielMemorial Sloan-Kettering Cancer CenterDepartment of Biochemistry, Swiss Federal Institute of Technology
  • , Josef BrunnerAffiliated withInstitute of Immunology, University of Kiel
  • , Paul SaftigAffiliated withInstitute of Immunology, University of Kiel
  • , Christoph PetersAffiliated withInstitute of Immunology, University of Kiel
  • , Martin KrönkeAffiliated withInstitute of Immunology, University of Kiel
    • , Stefan SchützeAffiliated withInstitute of Immunology, University of Kiel

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Abstract

We have identified the aspartic protease cathepsin D as a novel intracellular target protein for the lipid second messenger ceramide. Ceramide specifically binds to and induces CTSD proteolytic activity. A-SMase deficient cells derived from Niemann-Pick patients show decreased CTSD activity that was reconstituted by transfection with A-SMase cDNA. Ceramide accumulation in cells derived from A-ceramidase defective Farber patients correlates with enhanced CTSD activity. These findings suggest that A-SMase-derived ceramide targets endolysosomal CTSD.

Key words

Acid Sphingomyelinase Cathepsin D Ceramide TID-Ceramide