Lysosomal cathepsins in embryonic programmed cell death

Vanessa Zuzarte-Luis, Juan A. Montero, Yasuhiko Kawakami, Juan Carlos Izpisua Belmonte, Juan M. Hurle*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

During limb development, expression of cathepsin D and B genes prefigure the pattern of interdigital apoptosis including the differences between the chick and the webbed digits of the duck. Expression of cathepsin L is associated with advanced stages of degeneration. Analysis of Gremlin-/- and Dkk-/- mouse mutants and local treatments with BMP proteins reveal that the expression of cathepsin B and D genes is regulated by BMP signaling, a pathway responsible for triggering cell death. Further cathepsin D protein is upregulated in the preapoptotic mesenchyme before being released into the cytosol, and overexpression of cathepsin D induces cell death in embryonic tissues by a mechanism including mitochondrial permeabilization and nuclear translocation of AIF. Combined inhibition of cathepsin and caspases suggests a redundancy in the apoptotic molecular machinery, providing evidence for compensatory activation mechanisms in the cathepsin pathway when caspases are blocked. It is concluded that lysosomal enzymes are functionally implicated in embryonic programmed cell death.

Original languageEnglish (US)
Pages (from-to)205-217
Number of pages13
JournalDevelopmental Biology
Volume301
Issue number1
DOIs
StatePublished - Jan 1 2007

Keywords

  • AIF
  • Apoptosis
  • Caspase
  • Interdigital cell death
  • Limb development

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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