Inositol hexakisphosphate primes syndapin I/PACSIN 1 activation in endocytosis

Yue Shi, Kaixuan Zhao, Guang Yang, Jia Yu, Yuxin Li, Michael M Kessels, Lina Yu, Britta Qualmann, Per-Olof Berggren, Shao-Nian Yang

Research output: Contribution to journalArticlepeer-review

Abstract

Endocytosis is controlled by a well-orchestrated molecular machinery, where the individual players as well as their precise interactions are not fully understood. We now show that syndapin I/PACSIN 1 is expressed in pancreatic β cells and that its knockdown abrogates β cell endocytosis leading to disturbed plasma membrane protein homeostasis, as exemplified by an elevated density of L-type Ca2+ channels. Intriguingly, inositol hexakisphosphate (InsP6) activates casein kinase 2 (CK2) that phosphorylates syndapin I/PACSIN 1, thereby promoting interactions between syndapin I/PACSIN 1 and neural Wiskott-Aldrich syndrome protein (N-WASP) and driving β cell endocytosis. Dominant-negative interference with endogenous syndapin I/PACSIN 1 protein complexes, by overexpression of the syndapin I/PACSIN 1 SH3 domain, decreases InsP6-stimulated endocytosis. InsP6 thus promotes syndapin I/PACSIN 1 priming by CK2-dependent phosphorylation, which endows the syndapin I/PACSIN 1 SH3 domain with the capability to interact with the endocytic machinery and thereby initiate endocytosis, as exemplified in β cells.

Original languageEnglish
Article number286
Number of pages17
JournalCellular and Molecular Life Sciences
Volume79
Issue number6
Early online date9 May 2022
DOIs
Publication statusE-pub ahead of print - 9 May 2022

Bibliographical note

Funding Information:
Open access funding provided by Karolinska Institute. This work was supported by grants from Berth von Kantzow’s Foundation, the Deutsche Forschungsgemeinschaft (DFG), the ERC-2013-AdG 338936-Betalmage, the European Foundation for the Study of Diabetes, the Family Erling-Persson Foundation, Funds at Karolinska Institutet, Skandia Insurance Company, Ltd., the Stichting af Jochnick Foundation, Strategic Research Program in Diabetes at Karolinska Institutet, Swedish Alzheimer Association, the Swedish Diabetes Association, the Swedish Society of Medicine, the Swedish Research Council and the Novo Nordisk Foundation.

Publisher Copyright:
© 2022, The Author(s).

Keywords

  • Ca channel
  • Capacitance measurement
  • Casein kinase
  • Endocytosis
  • FM1-43 imaging
  • Syndapin/PACSIN

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