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  • The EMBO Journal (1999) 18, 5252 - 5263
  • doi:10.1093/emboj/18.19.5252



There is a Corrigendum (January 2000) associated with this Article.

Cathepsin D targeted by acid sphingomyelinase-derived ceramide

Michael Heinrich1,7, Marc Wickel1,7, Wulf Schneider-Brachert2, Christiane Sandberg1, Julie Gahr1, Ralf Schwandner3, Thomas Weber4,5, Josef Brunner4, Martin Krönke6 and Stefan Schütze1

  1. Institute of Immunology, University of Kiel, Kiel, Germany
  2. Present address: Institute of Medical Microbiology and Hygiene, University of Regensburg, Germany
  3. Present address: Tularik Inc., South San Francisco, CA 94080, USA
  4. Department of Biochemistry, Swiss Federal Institute of Technology, Zürich (ETHZ), Switzerland
  5. Present address: Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA
  6. Present address: Institute of Medical Microbiology and Hygiene, University of Cologne, Germany
  7. M.Heinrich and M.Wickel contributed equally to this work

Correspondence to:

Stefan Schütze, E-mail: schuetze@immunologie.uni-kiel.de

Received 12 April 1999; Accepted 3 August 1999; Revised 3 August 1999

Ceramide has been recognized as a common intracellular second messenger for various cytokines, growth factors and other stimuli, such as CD95, chemotherapeutic drugs and stress factors. To understand the role of ceramide during apoptosis and other cellular responses, it is critically important to characterize direct targets of ceramide action. In this paper, we show that ceramide specifically binds to and activates the endosomal acidic aspartate protease cathepsin D. Direct interaction of ceramide with cathepsin D results in autocatalytic proteolysis of the 52 kDa pre-pro cathepsin D to form the enzymatically active 48/32 kDa isoforms of cathepsin D. Acid sphingomyelinase (A-SMase)-deficient cells show decreased cathepsin D activity, which could be reconstituted by transfection with A-SMase cDNA. The results of our study identify cathepsin D as the first endosomal ceramide target that colocalizes with and may mediate downstream signaling effects of A-SMase.

  • Keywords:

    • acid sphingomyelinase,
    • cathepsin D,
    • ceramide,
    • TID-ceramide