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Processing and Intracellular Targeting of Somatostatin

  • Chapter
Somatostatin

Part of the book series: Endocrine Updates ((ENDO,volume 24))

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Summary

The intense interest in SST as a model to study neuropeptide synthesis has provided a framework for understanding the biosynthetic pathways, the putative role of PCs, and the secretory pathways required for PSST maturation to its active products. Kinetic studies have demonstrated that PSST is rapidly and independently processed to SST-14, SST-28, and PSST[1-10]. Both PC1 and PC2 are capable of processing PSST to SST-14. Furin and PACE 4 effect monobasic cleavage and are candidate SST-28 convertases. Contrary to previous belief, cleavage at the NH2-terminus has been shown not require the monobasic Lys13 residue with SKI-1 acting as the most likely convertase. Secretory granules are not a requirement for PSST maturation. Additionally, the conserved amino terminal segment of PSST serves as a sorting for the regulated secretory pathway. Beyond the pure biochemical and basic research interest in defining the specific intracellular events implicated in processing and sorting of PSST, combining the knowledge gained from the processing and targeting aspects to treatments of various diseases would be the ultimate satisfaction of any scientist. Such an approach was elegantly attempted by Rivera and colleagues who used the ER as the storage compartment for genetically engineered secretory proteins such as insulin and growth hormone (53).

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References

  1. Brazeau P, Vale W, Burgus R, Ling N, Butcher M, Rivier J, Guillemin R. Hypothalamic polypeptide that inhibits secretion of immunoreactive pituitary growth hormone. Science 1973; 179: 77–79.

    CAS  PubMed  Google Scholar 

  2. Goodman RH, Aron DC, Roos BA. Rat preprosomatostatin: structure and processing by microsomal membranes. J Biol Chem 1982; 258: 5570–5573.

    Google Scholar 

  3. Goodman RH, Jacobs JW, Chin W, Lund PK, Dee PC, Habener JF. Nucleotide sequence of a cloned structural gene coding for a precursor somatostatin. Proc Natl Acad Sci USA 1980; 77: 5869–5873.

    CAS  PubMed  Google Scholar 

  4. Hobart P, Crawford R, Shen L, Pictet R, Rutter WJ. Cloning and sequence analysis of cDNAs coding for two distinct somatostatin precursors found in the endocrine portion of anglerfish. Nature 1980; 288: 137–141.

    Article  CAS  PubMed  Google Scholar 

  5. Warren TG, Shields D. Cell-free biosynthesis of somatostatin precursors: evidence for multiple forms of preprosomatostatin. Proc Natl Acad Sci USA 1982; 79: 3729–3733.

    CAS  PubMed  Google Scholar 

  6. Shields D, Warren TG, Green RF, Roth SE, Brenner MJ. The primary events in the biosynthesis and post-translational processing of different precursors to somatostatin. In: Rich DH, Gross E, eds. Peptides: synthesis-structure-function: proceedings of the seventh American Peptide symposium. Rockford, III. Pirce Chemical Company, 1981: 471–479.

    Google Scholar 

  7. Patel YC, Wheatley T, Ning C. Multiple forms of immunoreactive somatostatin: comparison of distribution in neural and nonneural tissues and portal plasma of the rat. Endocrinology 1981; 109: 1943–1949.

    CAS  PubMed  Google Scholar 

  8. Baskin DG, Ensinck JW. Somatostatin in epithelial cells of intestinal mucosa present is present primarily as somatostatin-28. Peptides 1984; 5: 615–621.

    Article  CAS  PubMed  Google Scholar 

  9. Zhou, A., Webb, G., Zhu, X., and Steiner, D.F. Proteolytic processing in the secretory pathway. J Biol Chem 1999; 274: 20745–20748.

    CAS  PubMed  Google Scholar 

  10. Seidah NG, Chretein M. Proprotein and prohormone convertases: a family of subtilases generating diverse bioactive polypeptides Brain Res 1999; 848: 45–62.

    Article  CAS  PubMed  Google Scholar 

  11. Gluschankof P, Morel A, Gomez S, Nicolas P, Fahy C, Christine F, Cohen P. Enzymes processing somatostatin precursors: an Arg-Lys esteropeptidase from the rat brain cortex converting somatosatin-28 into somatostatin-14. Proc Natl Sci USA 1984; 81: 6662–6666.

    CAS  Google Scholar 

  12. Mackin RB, Noe BD. Direct evidence for two distinct prosomatostatin converting enzymes. J Biol Chem 1987; 262: 6453–6456.

    CAS  PubMed  Google Scholar 

  13. Mackin RB, Noe BD, Spiess J. Identification of a somatostatin-14 generating propeptide cnverting enzyme as a member of the kes2/furin/PC family. Endocrinology 1991; 129: 2263–2265.

    CAS  PubMed  Google Scholar 

  14. Galanopoulou AS, Kent G, Rabanni SN, Seidah NG, Patel YC. Heterologous processing of prosomatostatin in constitutive and regulated secretory pathways: Putative role of the endoproteases furin, PC1, and PC2. J Biol Chem 1993; 268:6041–9.

    CAS  PubMed  Google Scholar 

  15. Galanopoulou AS, Seidah NG, Patel YC. Heterologous processing of rat prosomatostatin to somatostatin-14 by PC2: requirement for secretory cell but not the secretion granule. Biochem J 1995; 311: 111–118.

    CAS  PubMed  Google Scholar 

  16. Marcinkeiwicz M, Ramala D, Seidah NG, Chretiem M. Developmemtal expression of the prohormoe convertases PC1 and PC2 in mouse pancreatic islets. Endocrinology 1994; 135: 1651–1660.

    Google Scholar 

  17. Furuta M, Yano H, Zhou A, Roulle Y, Hoist JJ, Carrol R, Ravazzola M, Orci L, Furuta H, Steiner DF. Defective prohormone processing and altered pancreatic islet morphology in mice lacking active SPC2. Proc Natl Acad Sci USA 1997; 94: 6646–6651.

    Article  CAS  PubMed  Google Scholar 

  18. Watanabe T, Nakagawa T, Lkemizu J, Nagahama M, Murakami K, Nakayama K. Sequence requirements for precursor cleavage within the constitutive secretory pathway. J Biol Chem 1992; 267: 8270–8274.

    CAS  PubMed  Google Scholar 

  19. Galanopoulou AS, Seidah NG, Patel YC. Direct role of furin in mammalian prosomatostatin processing. Biochem J 1995; 309: 33–40.

    CAS  PubMed  Google Scholar 

  20. Brakch N, Galanopoulou AS, Patel YC, Boileau G, Seidah NG. Comparative processing of rat prosomatostatin by the convertases PC1, PC2, furin, PACE4 and PC5 in constitutive and regulated secretory pathways. FEBS Lett 1995; 362: 143–146.

    Article  CAS  PubMed  Google Scholar 

  21. Brakch N, Rholam M, Boussetta A, Cohrn P. Role of beta-turn in proteolytic processing of peptide hormone precursors at dibasic sites Biochemistry 1993; 432: 4925–4930.

    Google Scholar 

  22. Rholam M, Nicholas P, Cohen P. Precursors for peptide hormones share common secondary structures forming features at the proteolytic processing sites. FEBS Lett 1986; 207: 1–6.

    Article  CAS  PubMed  Google Scholar 

  23. Brakch N, Lazar N, Panchal M, Allemandou F, Boileau G, Cohen P, Rholam M The Somatostatin-28(1–12)-NPAMAP sequence: an essential helical-promoting motif governing prosomatostatin processing at mono-and dibasic sites. Biochemistry 2002; 41: 1630–1639.

    Article  CAS  PubMed  Google Scholar 

  24. Benoit R, Ling N, Esch F. A new prosomatostatin-derived peptide reveals a pattern for prohormone cleavage at monobasic sites. Science 1987; 238: 1126–1129.

    CAS  PubMed  Google Scholar 

  25. Rabbani SN, Patel YC. Peptides derived by processing of rat prosomatostatin near the amino-terminus: characterization, tissue distribution and release. Endocrinology 1990; 126: 2054–2061.

    CAS  PubMed  Google Scholar 

  26. Ravazzola M, Benoit R, Orci L. Prosomatostatin-derived antrin is present in gastric D cells and in portal circulation. J Clin Invest 1989; 83: 362–366.

    CAS  PubMed  Google Scholar 

  27. Mouchantaf R, Sulea T, Seidah NG, and Kumar U. Prosomatostatin is proteolytically processed at the amino terminal segment by the subtilase SKI-1. Regulatory Peptides 2004 (submitted).

    Google Scholar 

  28. Sakai J, Rawson RB, Espenshade PJ, Cheng D, Seegmiller AC, Goldstein JL, Brown MS. Molecular identification of the sterol-regulated luminal protease that cleaves SREBPs and controls lipid metabolism. Mol Cell 1998; 2:505–514.

    Article  CAS  PubMed  Google Scholar 

  29. Seidah NG, Mowla SJ, Hamelin J, Mamarbachi AM, Benjannet S, Toure BB, Basak A, Munzer JS, Marcinkiewicz J, Zhong M, Barale JC, Lazure C, Murphy RA, Chretien M, Marcinkiewicz M. Mammalian subtilisin/kexin isozyme SKI-1: a widely expressed proprotein convertase with a unique cleavage specificity and cellular localization. Proc Natl Acad Sci USA 1999; 96: 1321–1326.

    Article  CAS  PubMed  Google Scholar 

  30. Ye J, Rawson RB, Komuro R, Chen X, Dave UP, Prywes R, Brown MS, Goldstein JL. ER stress induces cleavage of membrane-bound ATF6 by the same proteases that process SREBPs. Mol Cell 2000; 6: 1355–1364.

    Article  CAS  PubMed  Google Scholar 

  31. Lenz O, Meulen JT, Klenk HD, Seidah NG, Garten W. The Lassa virus glycoprotein precursor GP-C is proteolytically processed by subtilase SKI-1/S1P. Proc Natl Acad Sci USA 2001; 98: 12710–12705.

    Article  Google Scholar 

  32. Orci L, Ravazzola M, Storch MJ, Anderson RG, Vassalli JD, Perrelet A. Proteolytic maturation of insulin is a post-Golgi event which occurs in acidifying clathrin-coated secretory vesicles. Cell 1987; 49: 865–868.

    Article  CAS  PubMed  Google Scholar 

  33. Bourdais, J, Devillers G, Girard R, Morel A, Benedett L, Cohen P. Porsomatostatin II processing in the trans-Golgi network of anglerfish pancreatic cells. Biochem Biophys Res Commun 1990; 170: 1263–1271.

    Article  CAS  PubMed  Google Scholar 

  34. Lepage-Lezin A, Joseph-Bravo P, Devilliers G, Benedetti L, Launay J, Gomez S, Cohen P. Prosomatostatin is processed in eth Golgi apparatus of rat neural cells. J Biol Chem 1991; 266: 1679–1688.

    CAS  PubMed  Google Scholar 

  35. Xu H and Shields D. Prohormone processing in the trans-Golgi network: endoproteolytic cleavage of prosomatostatin and formation of nascent secretory vesicles in permeabilized cells. J Cell Biol 1993; 122: 1169–1184.

    Article  CAS  PubMed  Google Scholar 

  36. Patel YC, Galanopoulou AS, Rabanni SN, Liu JL, Ravazzola M, Amherdt M. Somatostatin-14, somatostatin-28, and prosomatostatin[1-10] are independently and efficiently processed from prosomatostatin in the constitutive secretory pathway in islet somatostatin tumour cells (1027B2). Mol Cell Endocrinol 1997; 131: 183–194.

    Article  CAS  PubMed  Google Scholar 

  37. Zingg HH, Patel YC. Biosynthesis of immunoreactive somatostatin by hypothalamic neurons in culture. J Clin Invest 1982; 70: 1101–1109.

    CAS  PubMed  Google Scholar 

  38. Aguila MC, Dees WL, Haensly WE, McCann SM. Evidence that somatostatin is localized and synthesized in lymphoid organs. Proc Natl Acad Sci USA 1991; 88: 11485–11489.

    CAS  PubMed  Google Scholar 

  39. Weinstock JV, Blum A, Malloy T. Macrophages within the granulomas of murine schistosomiasis mansoni are a source of a somatostatin 1–14 like molecule. Cell Immunol 1990; 131: 381–388.

    Article  CAS  PubMed  Google Scholar 

  40. Kelly RB. Pathways of protein secretion in eukaryotes. Science 1985; 230:25–32.

    CAS  PubMed  Google Scholar 

  41. Rothman JE, Orci L. Molecular dissection of the secretory pathway. Nature 1992; 355: 409–415.

    Article  CAS  PubMed  Google Scholar 

  42. Cool DR, Normant E, Shen ES, Chen HC, Pannell L, Zhang Y, Loh YP. Carboxypeptidase E is a regulated secretory pathway sorting receptor: genetic obliteration leads to endocrine disorders in Cpefat Mice. Cell 1997; 88: 73–83.

    Article  CAS  PubMed  Google Scholar 

  43. Normant E, Loh YP. Depletion of Carboxypeptidase E, a regulated secretory pathway sorting receptor, causes misrouting and constitutive secretion of proinsulin and proenkephalin, but not chromogranin A. Endocrinology 1998; 139: 2137–2145.

    Article  CAS  PubMed  Google Scholar 

  44. Tooze SA. Biogenesis of secretory granules in the trans-Golgi network of neuroendocrine and endocrine cells. Biochem Biophys Acta 1998; 1404: 231–244.

    CAS  PubMed  Google Scholar 

  45. Chung KN, Walter P, Aponte GW, Moore HP. Molecular sorting in the secretory pathway. Science 1988; 243: 192–197.

    Google Scholar 

  46. Kizer JS, Tropsha A. A motif found in propeptides that may target them to secretory vesicles. Biochem Biophys Res Commun 1991; 174: 586–592.

    Article  CAS  PubMed  Google Scholar 

  47. Patel YC. General aspects of the biology and function of somatostatin. In: Basic and Clinical Aspects of Neuroscience. Edited by C, Weil EE Muller, and MO Thorner. Berlin: Springer-Verlag 1992; 4:1–16.

    Google Scholar 

  48. Reichlin S, Saperstein R, Jackson IMD, Boyd AE, Patel YC. Hypothalamic hormone. Annu Rev Physiol 1976; 38: 389–424.

    Article  CAS  PubMed  Google Scholar 

  49. Sevarino KA, Stork P, Ventimiglia R, Mandel G, Goodman RH. Amino-terminal sequences of prosomatostatin direct intracellular targeting but not processing specificity. Cell 1989; 57: 11–19.

    Article  CAS  PubMed  Google Scholar 

  50. Shields D, Stoller T. The propeptide of preprosomatostatin mediates intracellular transport and secretion of α-globin from mammalian cells. J Cell Biol 1989; 108: 1647–1655.

    PubMed  Google Scholar 

  51. Sevarino KA, Stork P. Multiple preprosomatostatin sorting signals mediate secretion via discrete cAMP-and tetradecoylphorbolacetate-responsive pathways. J Biol Chem 1991; 266: 18507–18513.

    CAS  PubMed  Google Scholar 

  52. Mouchantaf R, Kumar U, Sulea T, and Patel YC. A conserved a helix at the amino terminal of prosomatostatin serves as a sorting signal for the regulated secretory pathway. J Biol Chem 2001; 276: 23308–23316.

    Article  Google Scholar 

  53. Rivera VM, Wang X, Wardwell S, Courage NL, Volchuk A, Keenan T, Holt DA, Gilman M, Orci L, Cerasoli F, Rothman JE, Clackson T. Regulation of protein secretion through controlled aggregation in the endoplasmic reticulum. Science 2000; 287: 826–830.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Fraser Laboratories, Departments of Medicine, Pharmacology and Therapeutics, Neurology and Neurosurgery, McGill University, Royal Victoria Hospital and Montreal Neurological Institute, Montreal, Quebec, Canada, H3A 1A1

    Rania Mouchantaf, Yogesh C. Patel & Ujendra Kumar

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  1. Rania Mouchantaf
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  2. Yogesh C. Patel
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  3. Ujendra Kumar
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Editors and Affiliations

  1. Department of Medicine, McGill University Heath Center, Montréal, Québec, Canada

    Coimbatore B. Srikant

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Mouchantaf, R., Patel, Y.C., Kumar, U. (2004). Processing and Intracellular Targeting of Somatostatin. In: Srikant, C.B. (eds) Somatostatin. Endocrine Updates, vol 24. Springer, Boston, MA. https://doi.org/10.1007/1-4020-8033-6_2

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  • DOI: https://doi.org/10.1007/1-4020-8033-6_2

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4020-7799-9

  • Online ISBN: 978-1-4020-8033-3

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