title: Lysosomal cathepsins in embryonic programmed cell death.
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.
authors.affiliation: Departamento de Anatomía y Biología Celular, Universidad de Cantabria, Facultad de Medicina, C/ Cardenal Herrera Oria s/n, Santander, Spain.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Zuzarte-Luis
authors.forename: Juan A
authors.initials: JA
authors.lastname: Montero
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Kawakami
authors.forename: Juan C
authors.initials: JC
authors.lastname: Izpisua-Belmonte
authors.forename: Juan M
authors.initials: JM
authors.lastname: Hurle
mesh_terms: D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002402:Cathepsin D / Q000378:metabolism*; D002642:Chick Embryo; D017931:DNA Primers; D004622:Embryo, Mammalian / Q000166:cytology*; D008247:Lysosomes / Q000201:enzymology*; D051379:Mice
chemical_list: D019485:Bone Morphogenetic Proteins; D017931:DNA Primers; D002402:Cathepsin D