Cathepsins Sculpt Toes

Science's STKE  02 Jan 2007:
Vol. 2007, Issue 367, pp. tw2
DOI: 10.1126/stke.3672007tw2

Digit formation involves massive programmed cell death. Zuzarte-Luis et al. show that in chicken embryo interdigital regions destined for cell death, the abundance of cathepsin D was increased, and in interdigit mesodermal cells, the enzyme transitions from a lysosomal localization to a cytosolic one as the cells begin to undergo cell death. Implantation of a bone morphogenetic protein (BMP) bead onto chicken or mouse embryo limbs resulted in increased expression of the cathepsin D gene in areas adjacent to the bead. A similar correlation between cathepsin B expression, BMP signaling, and regions destined for programmed cell death was noted. However, cathepsin L expression appeared at later stages of digit formation and was not increased by BMP beads. Cell death in the interdigital region was only effectively blocked if cultured limbs were exposed to both pepstatin A (a cathepsin D inhibitor) and a pan-caspase inhibitor. Cultured chicken cells overexpressing cathepsin D exhibited increased cell death, altered morphology, and nuclear translocation of apoptosis-inducing factor (AIF), which suggested that cathepsin D triggers mitochondrial permeabilization. The authors propose that, in tissues that require massive remodeling through cell death, both lysosomal enzymes and caspases contribute to the process.

V. Zuzarte-Luis, J. A. Montero, Y. Kawakami, J. C. Izpisua-Belmonte, J. M. Hurle, Lysosomal cathepsins in embryonic programmed cell death. Dev. Biol. 301, 205-217 (2007). [PubMed]