OVEREXPRESSION OF CATION-DEPENDENT MANNOSE 6-PHOSPHATE RECEPTOR PREVENTS CELL-DEATH INDUCED BY SERUM DEPRIVATION IN PC12 CELLS

PC12 cells express well cation-independent mannose 6-phosphate recepto rs (CI-MPR), but not cation-dependent (CD)-MPR as much. To examine CD- IMPR dependency of transport of cathepsins B and D to lysosomes in PC1 2 cells, we prepared the cells overexpressing CD-MPR. Immunoreactivity for cathepsin B became more distinct and larger in size in the transf ected cells than in wild-type cells. No difference in the distribution of cathepsin D was seen between these two cells. The viability of the cells following serum deprivation was significantly higher in the tra nsfected cells than in wild-type cells. This increased viability of th e transfected cells was blocked by CA074, a specific inhibitor of cath epsin B, while pepstatin A suppressed the action of CA074. The results suggest that CD-MPR preferentially transport cathepsin B in PC12 cell s, and cathepsins B and D participate in the regulation of PC12 cell a poptosis. (C) 1998 Academic Press.