Synaptotagmin-13 orchestrates pancreatic endocrine cell egression and islet morphogenesis
Mostafa Bakhti, Aimée Bastidas-Ponce, Sophie Tritschler, Oliver Czarnecki, Marta Tarquis-Medina, Eva Nedvedova, J Jaki, Stefanie J. Willmann, Katharina Scheibner, Perla Cota, Ciro Salinno, Karsten Boldt, Nicola Horn, Marius Ueffing, Ingo Burtscher, Fabian J. Theis, Ünal Coskun, Heiko Lickert
Abstract
-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.