Receptor-mediated targeting of hormones to secretory granules: role of carboxypeptidase E - PubMed (original) (raw)
Receptor-mediated targeting of hormones to secretory granules: role of carboxypeptidase E
Y P Loh et al. Trends Endocrinol Metab. 1997 May-Jun.
Abstract
Peptide hormones, neuropeptides, and other molecules such as the granins are specifically packaged into granules of the regulated secretory pathway and released in a calcium-dependent manner upon stimulation. Many of these molecules are synthesized as larger precursors (prohormones) that are processed to biologically active products within the granules. It has now become apparent that prohormones, proneuropeptides, and the granins contain conformation-dependent sorting signal motifs that facilitate their specific sorting and packaging into regulated secretory granules. Recently, a receptor to which these sorting signals bind has been identified as the membrane form of carboxypeptidase E (CPE) and localized to the Golgi apparatus, where sorting occurs, specifically at the trans-Golgi network. In this article, we review the evidence for a sorting signal-receptor-mediated mechanism for routing peptide hormones and prohormones to the regulated secretory granules. We also describe a mouse model, Cpe(fat), which has the CPE gene naturally mutated. Pituitary hormones were misrouted and secreted in an unregulated manner via the constitutive pathway in these Cpe(fat) mice, leading to endocrine disorders.
Similar articles
- Carboxypeptidase E is a regulated secretory pathway sorting receptor: genetic obliteration leads to endocrine disorders in Cpe(fat) mice.
Cool DR, Normant E, Shen F, Chen HC, Pannell L, Zhang Y, Loh YP. Cool DR, et al. Cell. 1997 Jan 10;88(1):73-83. doi: 10.1016/s0092-8674(00)81860-7. Cell. 1997. PMID: 9019408 - Lipid raft association of carboxypeptidase E is necessary for its function as a regulated secretory pathway sorting receptor.
Dhanvantari S, Loh YP. Dhanvantari S, et al. J Biol Chem. 2000 Sep 22;275(38):29887-93. doi: 10.1074/jbc.M005364200. J Biol Chem. 2000. PMID: 10896946 - Mechanism of sorting proopiomelanocortin and proenkephalin to the regulated secretory pathway of neuroendocrine cells.
Loh YP, Maldonado A, Zhang C, Tam WH, Cawley N. Loh YP, et al. Ann N Y Acad Sci. 2002 Oct;971:416-25. doi: 10.1111/j.1749-6632.2002.tb04504.x. Ann N Y Acad Sci. 2002. PMID: 12438160 Review. - Sorting mechanism of peptide hormones and biogenesis mechanism of secretory granules by secretogranin III, a cholesterol-binding protein, in endocrine cells.
Takeuchi T, Hosaka M. Takeuchi T, et al. Curr Diabetes Rev. 2008 Feb;4(1):31-8. doi: 10.2174/157339908783502406. Curr Diabetes Rev. 2008. PMID: 18220693 Review.
Cited by
- Effects of soluble CPE on glioma cell migration are associated with mTOR activation and enhanced glucose flux.
Ilina EI, Armento A, Sanchez LG, Reichlmeir M, Braun Y, Penski C, Capper D, Sahm F, Jennewein L, Harter PN, Zukunft S, Fleming I, Schulte D, Le Guerroué F, Behrends C, Ronellenfitsch MW, Naumann U, Mittelbronn M. Ilina EI, et al. Oncotarget. 2017 Jun 27;8(40):67567-67591. doi: 10.18632/oncotarget.18747. eCollection 2017 Sep 15. Oncotarget. 2017. PMID: 28978054 Free PMC article. - The extended granin family: structure, function, and biomedical implications.
Bartolomucci A, Possenti R, Mahata SK, Fischer-Colbrie R, Loh YP, Salton SR. Bartolomucci A, et al. Endocr Rev. 2011 Dec;32(6):755-97. doi: 10.1210/er.2010-0027. Epub 2011 Aug 23. Endocr Rev. 2011. PMID: 21862681 Free PMC article. Review. - 60 YEARS OF POMC: Biosynthesis, trafficking, and secretion of pro-opiomelanocortin-derived peptides.
Cawley NX, Li Z, Loh YP. Cawley NX, et al. J Mol Endocrinol. 2016 May;56(4):T77-97. doi: 10.1530/JME-15-0323. Epub 2016 Feb 15. J Mol Endocrinol. 2016. PMID: 26880796 Free PMC article. Review. - New roles of carboxypeptidase E in endocrine and neural function and cancer.
Cawley NX, Wetsel WC, Murthy SR, Park JJ, Pacak K, Loh YP. Cawley NX, et al. Endocr Rev. 2012 Apr;33(2):216-53. doi: 10.1210/er.2011-1039. Epub 2012 Mar 7. Endocr Rev. 2012. PMID: 22402194 Free PMC article. Review. - Ectopic expression of the neuropeptide pigment-dispersing factor alters behavioral rhythms in Drosophila melanogaster.
Helfrich-Förster C, Täuber M, Park JH, Mühlig-Versen M, Schneuwly S, Hofbauer A. Helfrich-Förster C, et al. J Neurosci. 2000 May 1;20(9):3339-53. doi: 10.1523/JNEUROSCI.20-09-03339.2000. J Neurosci. 2000. PMID: 10777797 Free PMC article.
LinkOut - more resources
Full Text Sources
Research Materials
Miscellaneous