Neuropeptide Processing and Its Impact on Melanocortin Pathways
| Autor: | Anne White, L E Pritchard |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Hypothalamo-Hypophyseal System
endocrine system medicine.medical_specialty Pro-Opiomelanocortin Neuropeptide Energy homeostasis Endocrinology Adrenocorticotropic Hormone Melanocortin receptor Proopiomelanocortin Skin Physiological Phenomena Internal medicine medicine Animals Humans Obesity Secretory pathway biology Body Weight Neuropeptides digestive oral and skin physiology Proprotein convertase Melanocortins Neuropeptide processing nervous system biology.protein Melanocortin Protein Processing Post-Translational hormones hormone substitutes and hormone antagonists |
| Zdroj: | Endocrinology. 148:4201-4207 |
| ISSN: | 1945-7170 0013-7227 |
| DOI: | 10.1210/en.2006-1686 |
| Popis: | Proopiomelanocortin (POMC) is processed in an intracellular secretory pathway, primarily to enable release of ACTH from the pituitary and alpha-MSH from hypothalamic neurons and skin. However, processing is incomplete and unprocessed POMC is secreted from all three tissues. This review considers intracellular processing of neuronal POMC as a key checkpoint that controls flux through hypothalamic melanocortin receptor pathways. Regulation of the convertase, proprotein convertase (PC)-1/3, which cleaves POMC is likely to determine the extent of POMC processing. Reduced PC1/3 activity, in both humans and rodents, leads to reduced melanocortin signaling and hence obesity. In contrast to POMC, posttranslational processing of proagouti-related peptide, an endogenous melanocortin-4 receptor antagonist, is efficient and is unlikely to represent a regulatory checkpoint. Because POMC is fully processed to ACTH and MSH peptides in secretory vesicles, unprocessed POMC, which is released from cells, must exit via an unregulated constitutive pathway. Therefore, the targeting of POMC to secretory granules controls the extent of POMC cleavage. There is evidence that PC1/3 is involved in cleavage of POMC in the trans-Golgi network and regulation of trafficking to the secretory pathway, in which it subsequently cleaves POMC to the melanocortin peptides. This would suggest that alpha-MSH and beta-MSH may be subject to alternative sorting mechanisms, leading to heterogeneity in secretory granule content in POMC-producing cells. Overall, these studies implicate POMC processing as a key regulatory mechanism in the control of energy homeostasis. |
| Databáze: | OpenAIRE |
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