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Synaptotagmin-13 orchestrates pancreatic endocrine cell egression and islet morphogenesis.

Nat. Commun. 13:4540 (2022)
Verlagsversion Forschungsdaten Forschungsdaten Forschungsdaten DOI
Open Access Gold
Creative Commons Lizenzvertrag
During pancreas development endocrine cells leave the ductal epithelium to form the islets of Langerhans, but the morphogenetic mechanisms are incompletely understood. Here, we identify the Ca2+-independent atypical Synaptotagmin-13 (Syt13) as a key regulator of endocrine cell egression and islet formation. We detect specific upregulation of the Syt13 gene and encoded protein in endocrine precursors and the respective lineage during islet formation. The Syt13 protein is localized to the apical membrane of endocrine precursors and to the front domain of egressing endocrine cells, marking a previously unidentified apical-basal to front-rear repolarization during endocrine precursor cell egression. Knockout of Syt13 impairs endocrine cell egression and skews the α-to-β-cell ratio. Mechanistically, Syt13 is a vesicle trafficking protein, transported via the microtubule cytoskeleton, and interacts with phosphatidylinositol phospholipids for polarized localization. By internalizing a subset of plasma membrane proteins at the front domain, including α6β4 integrins, Syt13 modulates cell-matrix adhesion and allows efficient endocrine cell egression. Altogether, these findings uncover an unexpected role for Syt13 as a morphogenetic driver of endocrinogenesis and islet formation.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Zeitschrift Nature Communications
Quellenangaben Band: 13, Heft: 1, Seiten: , Artikelnummer: 4540 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes and Regeneration Research (IDR)
Institute of Computational Biology (ICB)
Institute for Pancreatic Beta Cell Research (IPI)
Förderungen Tistou & Charlotte Kerstan Stiftung
DZD, DZD-Next funding
Helmholtz Association-Initiative and Networking Fund (IVF)
German Center for Diabetes Research (DZD e.V.)
German Research Foundation (DFG)
Helmholtz Portfolio Theme'Metabolic Dysfunction and Common Disease
Helmholtz Association