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Title:Intracellular serotonin modulates insulin secretion from pancreatic ß-cells by protein serotonylation
Authors:ID Paulmann, Nils (Author)
ID Grohmann, Maik (Author)
ID Voigt, Jörg-Peter (Author)
ID Bert, Bettina (Author)
ID Vowinckel, Jakob (Author)
ID Bader, Michael (Author)
ID Skelin, Maša (Author)
ID Jevšek, Marko (Author)
ID Fink, Heidrun (Author)
ID Rupnik, Marjan (Author)
ID Walther, Diego (Author)
Files:.pdf PLoS_Biology_2009_Paulmann_et_al._Intracellular_Serotonin_Modulates_Insulin_Secretion_from_Pancreatic_β-Cells_by_Protein_Serotonylation.PDF (774,75 KB)
MD5: 94CEBC5DBC3F2093108FCABC615596B9
 
URL http://dx.plos.org/10.1371/journal.pbio.1000229
 
Language:English
Work type:Scientific work
Typology:1.01 - Original Scientific Article
Organization:MF - Faculty of Medicine
Abstract:While serotonin (5-HT) co-localization with insulin in granules of pancreatic ß-cells was demonstrated more than three decades ago, its physiological role in the etiology of diabetes is stili unclear. We combined biochemical and electrophysiological analyses of mice selectively deficient in peripheral tryptophan hydroxylase (Tph1-/-) and 5-HT to show that intracellular 5-HT regulates insulin secretion. We found that these mice are diabetic and have an impaired insulin secretion due to the lack of 5-HT in the pancreas. The pharmacological restoration of peripheral 5-HT levels rescued the impaired insulin secretion in vivo. These findings were further evidenced by patch clamp experiments with isolated Tph1-/- ß-cells, which clearly showed that the secretory defect is downstream of Ca2+ -signaling and can be rescued by direct intracellular application of 5-HT via the clamp pipette. In elucidating the underlying mechanism further, we demonstrate the covalent coupling of 5-HT by transglutaminases during insulin exocytosis to two key players in insulin secretion, the small GTPases Rab3a and Rab27a. This renders them constitutively active in a receptor-independent signaling mechanism we have recently termed serotonylation. Concordantly, an inhibition of such activating serotonylation in ß-cells abates insulin secretion. We also observed inactivation of serotonylated Rab3a by enhanced proteasomal degradation, which is in line with the inactivation of other serotonylated GTPases. Our results demonstrate that 5-HT regulates insulin secretion by serotonylation of GTPases within pancreatic ß-cells and suggest that intracellular 5-HT functions in various microenvironments via this mechanism in concert with the known receptor-mediated signaling.
Keywords:insulin secretion, serotonin, insulin, glucose, diabetes mellitus, guanosine triphosphatase, exocytosis, pancreas
Publication status:Published
Publication version:Version of Record
Year of publishing:2009
Number of pages:str. 1-10
Numbering:Letn. 7, št. 10
PID:20.500.12556/DKUM-66246 New window
ISSN:1544-9173
UDC:612
ISSN on article:1544-9173
COBISS.SI-ID:63941377 New window
DOI:10.1371/journal.pbio.1000229 New window
NUK URN:URN:SI:UM:DK:6HWSMNH2
Publication date in DKUM:16.06.2017
Views:2195
Downloads:202
Metadata:XML DC-XML DC-RDF
Categories:Misc.
:
PAULMANN, Nils, GROHMANN, Maik, VOIGT, Jörg-Peter, BERT, Bettina, VOWINCKEL, Jakob, BADER, Michael, SKELIN, Maša, JEVŠEK, Marko, FINK, Heidrun, RUPNIK, Marjan and WALTHER, Diego, 2009, Intracellular serotonin modulates insulin secretion from pancreatic ß-cells by protein serotonylation. PLoS Biology [online]. 2009. Vol. 7, no. 10, p. 1–10. [Accessed 17 April 2025]. DOI 10.1371/journal.pbio.1000229. Retrieved from: https://dk.um.si/IzpisGradiva.php?lang=eng&id=66246
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Record is a part of a journal

Title:PLoS Biology
Shortened title:PLoS Biol.
Publisher:Public Library of Science
ISSN:1544-9173
COBISS.SI-ID:512779289 New window

Licences

License:CC BY 4.0, Creative Commons Attribution 4.0 International
Link:http://creativecommons.org/licenses/by/4.0/
Description:This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
Licensing start date:16.06.2017

Secondary language

Language:Slovenian
Keywords:izločanje inzulina, serotonin, inzulin, glukoza, sladkorna bolezen, diabetes mellitus, gvanozin-trifosfataza, eksocitoza, pankreas, trebušna slinavka


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