Journal article
Procorticotrophin-releasing hormone: endoproteolytic processing and differential release of its derived peptides within AtT20 cells
Molecular and Cellular Endocrinology, Vol.142(1), pp.191-202
1998
PMID: 9783915
Abstract
Procorticotrophin-releasing hormone (proCRH) is expressed mainly in the hypothalamus and in the placenta, where it undergoes tissue-specific endoproteolysis. Our results show that within stably transfected AtT20/D16V cells proCRH is cleaved to generate two fragments of ≈8 and 3 kDa which could account for proCRH(125–194) and proCRH(125–151), respectively, and a 4.5 kDa product which could account for mature IR-CRH(1–41). The immunofluorescence staining patterns for IR-CRH and IR-ACTH and their response of secretagogues indicate targeting of proCRH and POMC to the secretory pathway in transfected AtT20 cells. In this work, we have used a unique set of specific RIAs and IRMAs to the full length POMC and proCRH molecules and several products of endoproteolytic processing to assess if they could be released differentially in response to stimulation. Although the release of both IR-ACTH and IR-CRH peptides from transfected AtT20 cells is stimulated in response to exposure to high potassium stimulation (51 mM KCl/5mM CaCl
2), the sorting index (SI) suggests that mature ACTH is sorted to the regulated secretory pathway 2.1-fold more efficiently than mature CRH(1–41). Mature ACTH is also sorted to the regulated secretory pathway 9-fold more efficiently than IR-proCRH(125–151). Also, mature CRH(1–41) is sorted to the regulated secretory pathway 3-fold more efficiently than IR-proCRH(125–151). These results therefore indicate that the intracellular mechanisms for the storage and release of POMC, proCRH and their endoproteolytic products differ and would sustain the hypothesis that within mammalian peptidergic cells, different biologically active peptides originating from the same or different precursor molecules, could be differentially released in response to specific stimuli. This would give these cells the capacity to finely regulate neurotransmitter release in response to environmental and physiological demands.
Details
- Title
- Procorticotrophin-releasing hormone: endoproteolytic processing and differential release of its derived peptides within AtT20 cells
- Authors
- M.J Perone (Author) - University of ManchesterC.A Murray (Author) - University of ManchesterO.A Brown (Author) - University of ManchesterS Gibson (Author) - University of ManchesterA White (Author) - University of ManchesterE.A Linton (Author) - University of OxfordA.V Perkins (Author) - University of OxfordP.R Lowenstein (Author) - University of ManchesterM.G Castro (Corresponding Author) - University of Manchester
- Publication details
- Molecular and Cellular Endocrinology, Vol.142(1), pp.191-202
- Publisher
- Elsevier Ireland Ltd
- DOI
- 10.1016/S0303-7207(98)00104-X
- ISSN
- 1872-8057
- PMID
- 9783915
- Organisation Unit
- School of Health and Behavioural Sciences - Legacy; School of Health
- Language
- English
- Record Identifier
- 99685296702621
- Output Type
- Journal article
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- Endocrinology & Metabolism
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