Sorting mechanism of peptide hormones and biogenesis mechanism of secretory granules by secretogranin III, a cholesterol-binding protein, in endocrine cells

Curr Diabetes Rev. 2008 Feb;4(1):31-8. doi: 10.2174/157339908783502406.


In the present review, we discuss the sorting mechanism of peptide hormones and the biogenesis mechanism of secretory granules in view of the significance of the high cholesterol composition of secretory granule membranes. Peptide hormones and granin-family proteins are sorted to immature budding granules at the trans-Golgi network in neuroendocrine cells. Two models have been proposed for granule protein sorting: "aggregation-mediated sorting" and "receptor-mediated sorting". In the aggregation-mediated sorting model, granin-family proteins such as chromogranin A and B form aggregates with peptide hormones in weakly acidic, high calcium milieu of the budding granules. Chromogranins have a disulfide loop at their N-terminal at which they bind to the budding granular membrane, and bring hormones to the granules. In the receptor-mediated sorting model, carboxypeptidase E and/or secretogranin III function as a sorting receptor for peptide hormones. They bind peptide hormones, such as proopiomelanocortin, and have a high-cholesterol-binding domain. Since secretory granule membranes contain high levels of cholesterol, peptide hormones are brought to the secretory granules by these receptors. Although the two models have been conflicting, we suggest that both are cooperative and compensating each other for the sorting of peptide hormones and the biogenesis of secretory granules.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Carboxypeptidase H / metabolism
  • Chromogranin A / physiology
  • Chromogranins / physiology*
  • Endoplasmic Reticulum / physiology
  • Humans
  • Insulin-Secreting Cells / physiology
  • Neuroendocrine Cells / physiology
  • Peptide Hormones / biosynthesis
  • Peptide Hormones / physiology*
  • Proinsulin / biosynthesis
  • Protein Precursors / physiology
  • Secretory Vesicles / physiology*


  • Chromogranin A
  • Chromogranins
  • Peptide Hormones
  • Protein Precursors
  • secretogranin III
  • Proinsulin
  • Carboxypeptidase H