Cathepsin D in pancreatic acinar cells is implicated in cathepsin B and L degradation, but not in autophagic activity.

ABSTRACT

Cathepsin D (CD) is the major lysosomal aspartic protease and is widely distributed in the cells of various mammalian tissues. CD participates in various physiological events such as regulation of programmed cell death, activation of enzymatic precursors, and metabolic degradation of intracellular proteins through macroautophagy. To investigate the role of CD in pancreatic acinar cells, which constitute the exocrine pancreas, we generated and examined mice specifically deficient for CD in pancreatic acinar cells. CD deficient mice showed normal pancreatic development and autophagic activity, although LC3-II, which is a marker of the autophagosome, accumulates in both physiological and pancreatitis conditions. Moreover, CD deficiency leads to accumulation of matured cathepsin B (CB) and cathepsin L (CL) which are members of the cysteine protease family. We therefore conclude that CD in pancreatic acinar cells is implicated in CB and CL degradation but not in autophagic activity.