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Synaptotagmin-13 orchestrates pancreatic endocrine cell egression and islet morphogenesis

Author

Listed:
  • Mostafa Bakhti

    (Helmholtz Zentrum München
    German Center for Diabetes Research (DZD))

  • Aimée Bastidas-Ponce

    (Helmholtz Zentrum München
    German Center for Diabetes Research (DZD))

  • Sophie Tritschler

    (Helmholtz Zentrum München
    Helmholtz Zentrum München
    Technical University of Munich, School of Life Sciences Weihenstephan)

  • Oliver Czarnecki

    (Helmholtz Zentrum München
    German Center for Diabetes Research (DZD)
    Technische Universität München, School of Medicine)

  • Marta Tarquis-Medina

    (Helmholtz Zentrum München
    German Center for Diabetes Research (DZD)
    Technische Universität München, School of Medicine)

  • Eva Nedvedova

    (German Center for Diabetes Research (DZD)
    Paul Langerhans Institute Dresden of the Helmholtz Zentrum Munich at the University Clinic Carl Gustav Carus, TU Dresden
    SOTIO a.s, Jankovcova 1518/2)

  • Jessica Jaki

    (Helmholtz Zentrum München
    German Center for Diabetes Research (DZD))

  • Stefanie J. Willmann

    (Helmholtz Zentrum München)

  • Katharina Scheibner

    (Helmholtz Zentrum München
    German Center for Diabetes Research (DZD))

  • Perla Cota

    (Helmholtz Zentrum München
    German Center for Diabetes Research (DZD)
    Technische Universität München, School of Medicine)

  • Ciro Salinno

    (Helmholtz Zentrum München
    German Center for Diabetes Research (DZD)
    Technische Universität München, School of Medicine)

  • Karsten Boldt

    (University of Tübingen)

  • Nicola Horn

    (University of Tübingen)

  • Marius Ueffing

    (University of Tübingen)

  • Ingo Burtscher

    (Helmholtz Zentrum München
    German Center for Diabetes Research (DZD))

  • Fabian J. Theis

    (Helmholtz Zentrum München
    Technical University of Munich, Department of Mathematics, Garching b)

  • Ünal Coskun

    (German Center for Diabetes Research (DZD)
    Paul Langerhans Institute Dresden of the Helmholtz Zentrum Munich at the University Clinic Carl Gustav Carus, TU Dresden
    Technische Universität Dresden)

  • Heiko Lickert

    (Helmholtz Zentrum München
    German Center for Diabetes Research (DZD)
    Technische Universität München, School of Medicine)

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.

Suggested Citation

  • Mostafa Bakhti & Aimée Bastidas-Ponce & Sophie Tritschler & Oliver Czarnecki & Marta Tarquis-Medina & Eva Nedvedova & Jessica Jaki & Stefanie J. Willmann & Katharina Scheibner & Perla Cota & Ciro Sali, 2022. "Synaptotagmin-13 orchestrates pancreatic endocrine cell egression and islet morphogenesis," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31862-8
    DOI: 10.1038/s41467-022-31862-8
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    References listed on IDEAS

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