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Related Experiment Video

Updated: Jul 14, 2026

Pharmacologic Induction of Epidermal Melanin and Protection Against Sunburn in a Humanized Mouse Model
12:37

Pharmacologic Induction of Epidermal Melanin and Protection Against Sunburn in a Humanized Mouse Model

Published on: September 7, 2013

Neuropeptide processing and its impact on melanocortin pathways.

Lynn E Pritchard1, Anne White

  • 1Endocrine Sciences, University of Manchester, UCTF Building, 46 Grafton Street, Manchester M13 9NT, United Kingdom.

Endocrinology
|June 23, 2007
PubMed
Summary

Proopiomelanocortin (POMC) processing, regulated by PC1/3 convertase, controls melanocortin signaling. Impaired POMC processing leads to reduced signaling and obesity, highlighting its role in energy homeostasis.

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Multi-Faceted Mass Spectrometric Investigation of Neuropeptides in Callinectes sapidus

Published on: May 31, 2022

Area of Science:

  • Neuroendocrinology
  • Molecular Biology
  • Metabolic Regulation

Background:

  • Proopiomelanocortin (POMC) is a precursor protein processed into various peptides, including ACTH and melanocyte-stimulating hormone (MSH) alpha and beta.
  • POMC processing occurs within the intracellular secretory pathway, but is often incomplete, leading to secretion of unprocessed POMC.
  • Melanocortin pathways, regulated by POMC-derived peptides, play a crucial role in energy homeostasis.

Purpose of the Study:

  • To review the role of intracellular POMC processing as a regulatory checkpoint in hypothalamic melanocortin pathways.
  • To investigate the impact of proprotein convertase (PC)-1/3 activity on POMC processing and melanocortin signaling.
  • To explore the mechanisms controlling POMC targeting to secretory granules and its implications for peptide release.

Main Methods:

  • Review of existing literature on POMC processing, convertase activity, and melanocortin receptor signaling.
  • Analysis of studies in human and rodent models with altered PC1/3 activity.
  • Examination of evidence regarding the intracellular trafficking and sorting of POMC and its processing enzymes.

Main Results:

  • Intracellular processing of POMC is a critical checkpoint controlling hypothalamic melanocortin receptor pathway flux.
  • Reduced activity of the PC1/3 convertase impairs POMC processing, leading to diminished melanocortin signaling and obesity in humans and rodents.
  • Unlike POMC, proagouti-related peptide processing is efficient and not considered a regulatory checkpoint.
  • Unprocessed POMC is secreted via a constitutive pathway, indicating that targeting POMC to secretory granules regulates cleavage extent.
  • PC1/3 activity in the trans-Golgi network influences POMC trafficking and cleavage, potentially leading to heterogeneous secretory granule content.

Conclusions:

  • POMC processing is a key regulatory mechanism governing energy homeostasis.
  • The activity of PC1/3 is a critical determinant of POMC processing and subsequent melanocortin signaling.
  • Targeting of POMC to secretory granules and its cleavage by PC1/3 are central to regulating the release of MSH peptides and controlling energy balance.