The proprotein convertases in the murine small intestine

Abstract

The small intestine (SI) is a major endocrine organ with over 40 precursor hormones produced and proteolytically matured into active peptide hormones which signal throughout the body including the pancreas and CNS. One group of enzymes believed to be responsible for this maturation is the family of protein convertases (PCSKs). Using double immunofluorescent microscopy, the spatial localization of PCSK1, 2 and 3 in each region of the SI and colocalization with potential intestinal substrates was examined in mice. A unique regional expression pattern was observed for each of the PCSKs and several hormones examined exhibited high levels of colocalization. Next the gastrointestinal physiology of the PCSK2 knock out (KO) mouse was examined and correlated with the circulating levels of hormones known to mediate these functions. KO animals consume less food immediately after refeeding and have delayed intestinal transit. Several of the hormones responsible for feeding and intestinal motility were modulated in the PCSK KO animals. These studies suggest that the PCSK1 2 and 3 are present in the SI and required for normal functionality.