Synaptotagmin-13 orchestrates pancreatic endocrine cell egression and islet morphogenesis

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Mostafa Bakhti - , Helmholtz Centre for Environmental Research, German Center for Diabetes Research (Author)
  • Aimée Bastidas-Ponce - , Helmholtz Centre for Environmental Research, German Center for Diabetes Research (Author)
  • Sophie Tritschler - , Helmholtz Centre for Environmental Research, Technical University of Munich (Author)
  • Oliver Czarnecki - , Helmholtz Centre for Environmental Research, German Center for Diabetes Research, Technical University of Munich (Author)
  • Marta Tarquis-Medina - , Helmholtz Centre for Environmental Research, German Center for Diabetes Research, Technical University of Munich (Author)
  • Eva Nedvedova - , German Center for Diabetes Research, Technische Universität Dresden, Jankovcova 1518/2 (Author)
  • Jessica Jaki - , Helmholtz Centre for Environmental Research, German Center for Diabetes Research (Author)
  • Stefanie J. Willmann - , Helmholtz Centre for Environmental Research (Author)
  • Katharina Scheibner - , Helmholtz Centre for Environmental Research, German Center for Diabetes Research (Author)
  • Perla Cota - , Helmholtz Centre for Environmental Research, German Center for Diabetes Research, Technical University of Munich (Author)
  • Ciro Salinno - , Helmholtz Centre for Environmental Research, German Center for Diabetes Research, Technical University of Munich (Author)
  • Karsten Boldt - , University of Tübingen (Author)
  • Nicola Horn - , University of Tübingen (Author)
  • Marius Ueffing - , University of Tübingen (Author)
  • Ingo Burtscher - , Helmholtz Centre for Environmental Research, German Center for Diabetes Research (Author)
  • Fabian J. Theis - , Helmholtz Centre for Environmental Research, Technical University of Munich (Author)
  • Ünal Coskun - , University Medicine (Faculty of Medicine and University Hospital), Institute of Clinical Chemistry and Laboratory Medicine, German Center for Diabetes Research, Center of Membrane Biochemistry and Lipid Research (Author)
  • Heiko Lickert - , Helmholtz Centre for Environmental Research, German Center for Diabetes Research, Technical University of Munich (Author)

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.

Details

Original languageEnglish
Article number4540
JournalNature communications
Volume13
Issue number1
Publication statusPublished - Dec 2022
Peer-reviewedYes

External IDs

PubMed 35927244

Keywords

Keywords

  • Endocrine Cells, Integrins, Islets of Langerhans, Morphogenesis, Pancreas, Synaptotagmins/genetics