Molecular cloning and characterization of NESP55, a novel chromogranin- like precursor of a peptide with 5-HT(1B) receptor antagonist activity

Rudolf Ischia, Paola Lovisetti-Scamihorn, Ruth Hogue-Angeletti, Martin Wolkersdorfer, Hans Winkler, Reiner Fischer-Colbrie

Research output: Contribution to journalArticle

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Abstract

The chromogranins comprise a class of acidic proteins that are secreted from large dense core vesicles and expressed in neuronal and endocrine tissues. We describe here the molecular characterization of NESP55 (neuroendocrine secretory protein of M(r) 55,000), a novel member of the chromogranins. Several NESP55 cDNA clones were isolated from bovine chromaffin cell libraries. The cDNA sequence of NESP55 totals 1499 nucleotides. All of the clones that were isolated contained in their 3'- untranslated mRNA a sequence that was homologous to exon 2 of the G-protein G(s)α. The open reading frame encodes for an acidic and hydrophilic protein of 241 amino acids with a predicted molecular mass of 27,494 Da. An antiserum directed against the C terminus of NESP55 labeled a band of M(r) 55,000 with an acidic pI ranging from 4.4 to 5.2 in one- and two-dimensional immunoblots of secretory proteins from chromaffin granules. NESP55 is localized within the cell to the large dense secretory vesicles and is expressed, apart from the adrenal medulla, in the anterior and posterior pituitary and various regions of the brain. For the physiological function, one interesting factor has emerged. NESP55 is proteolytically processed within the chromaffin granule to smaller peptides that might be physiologically active. One tetrapeptide, Leu-Ser-Ala-Leu (LSAL), present in the NESP55 sequence and flanked by arginine residues suitable for cleavage by prohormone convertases, has been identified recently as an endogenous antagonist of the serotonergic 5-HT1(B) receptor subtype. Alterations in the serotonergic system are thought to play an important role in mental disorders, especially depression, and might be related to abnormal ethanol consumption. It is tempting to speculate that increased expression of NESP55 or its proteolytically derived peptide LSAL might contribute to the pathophysiology of the serotonergic transmission.

Original languageEnglish (US)
Pages (from-to)11657-11662
Number of pages6
JournalJournal of Biological Chemistry
Volume272
Issue number17
DOIs
StatePublished - Apr 25 1997

Fingerprint

Receptor, Serotonin, 5-HT1B
Chromogranins
Cloning
Molecular Cloning
5-HT-moduline
Chromaffin Granules
Peptides
Secretory Vesicles
Proteins
Complementary DNA
Clone Cells
Serotonin 5-HT1 Receptors
Proprotein Convertases
Chromaffin Cells
Adrenal Medulla
Molecular mass
Sequence Homology
GTP-Binding Proteins
Mental Disorders
Open Reading Frames

ASJC Scopus subject areas

  • Biochemistry

Cite this

Ischia, R., Lovisetti-Scamihorn, P., Hogue-Angeletti, R., Wolkersdorfer, M., Winkler, H., & Fischer-Colbrie, R. (1997). Molecular cloning and characterization of NESP55, a novel chromogranin- like precursor of a peptide with 5-HT(1B) receptor antagonist activity. Journal of Biological Chemistry, 272(17), 11657-11662. https://doi.org/10.1074/jbc.272.17.11657

Molecular cloning and characterization of NESP55, a novel chromogranin- like precursor of a peptide with 5-HT(1B) receptor antagonist activity. / Ischia, Rudolf; Lovisetti-Scamihorn, Paola; Hogue-Angeletti, Ruth; Wolkersdorfer, Martin; Winkler, Hans; Fischer-Colbrie, Reiner.

In: Journal of Biological Chemistry, Vol. 272, No. 17, 25.04.1997, p. 11657-11662.

Research output: Contribution to journalArticle

Ischia, R, Lovisetti-Scamihorn, P, Hogue-Angeletti, R, Wolkersdorfer, M, Winkler, H & Fischer-Colbrie, R 1997, 'Molecular cloning and characterization of NESP55, a novel chromogranin- like precursor of a peptide with 5-HT(1B) receptor antagonist activity', Journal of Biological Chemistry, vol. 272, no. 17, pp. 11657-11662. https://doi.org/10.1074/jbc.272.17.11657
Ischia, Rudolf ; Lovisetti-Scamihorn, Paola ; Hogue-Angeletti, Ruth ; Wolkersdorfer, Martin ; Winkler, Hans ; Fischer-Colbrie, Reiner. / Molecular cloning and characterization of NESP55, a novel chromogranin- like precursor of a peptide with 5-HT(1B) receptor antagonist activity. In: Journal of Biological Chemistry. 1997 ; Vol. 272, No. 17. pp. 11657-11662.
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