Proglucagon sorting in endocrine cells

Proglucagon is expressed in pancreatic alpha cells, intestinal L cells and brainstem neurons. Tissue-specific processing of proglucagon yields the peptide hormones glucagon in the alpha cell and glucagon-like peptide (GLP)-1 and GLP-2 in L cells. Both glucagon and GLP-1 are secreted in response to nutritional status and are critical for regulating glycaemia. While many studies have described the tissue-specific, post-translational processing of proglucagon, and elucidated the mechanisms underlying the regulation of glucagon and GLP-1 secretion, the mechanisms by which proglucagon is sorted into secretory granules remain unidentified.

Sorting is a critical step in the proglucagon biosynthetic pathway and therefore, McGhirr et al. sought to determine some possible mechanisms by which proglucagon is sorted into granules. They examined the roles of carboxypeptidase E (CPE), a prohormone sorting receptor, the processing enzymes PC1/3 and PC2 and putative intrinsic sorting signals in proglucagon sorting.

They conclude that there are multiple mechanisms for sorting proglucagon to the regulated secretory pathway, including a role for CPE in pancreatic alpha cells, initial cleavage at K70R71 and multiple sorting signals.

Read the full article in McGhirr et al (2013) Journal of Endocrinology 217 229-240 DOI: 10.1530/JOE-12-0468