Synaptotagmin-13 orchestrates pancreatic endocrine cell egression and islet morphogenesis

Mostafa Bakhti (), Aimée Bastidas-Ponce, Sophie Tritschler, Oliver Czarnecki, Marta Tarquis-Medina, Eva Nedvedova, Jessica Jaki, Stefanie J. Willmann, Katharina Scheibner, Perla Cota, Ciro Salinno, Karsten Boldt, Nicola Horn, Marius Ueffing, Ingo Burtscher, Fabian J. Theis, Ünal Coskun and Heiko Lickert ()
Additional contact information
Mostafa Bakhti: Helmholtz Zentrum München
Aimée Bastidas-Ponce: Helmholtz Zentrum München
Sophie Tritschler: Helmholtz Zentrum München
Oliver Czarnecki: Helmholtz Zentrum München
Marta Tarquis-Medina: Helmholtz Zentrum München
Eva Nedvedova: German Center for Diabetes Research (DZD)
Jessica Jaki: Helmholtz Zentrum München
Stefanie J. Willmann: Helmholtz Zentrum München
Katharina Scheibner: Helmholtz Zentrum München
Perla Cota: Helmholtz Zentrum München
Ciro Salinno: Helmholtz Zentrum München
Karsten Boldt: University of Tübingen
Nicola Horn: University of Tübingen
Marius Ueffing: University of Tübingen
Ingo Burtscher: Helmholtz Zentrum München
Fabian J. Theis: Helmholtz Zentrum München
Ünal Coskun: German Center for Diabetes Research (DZD)
Heiko Lickert: Helmholtz Zentrum München

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: Abstract 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.

Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31862-8

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DOI: 10.1038/s41467-022-31862-8

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