Journal
CELLULAR AND MOLECULAR LIFE SCIENCES
Volume 79, Issue 6, Pages -Publisher
SPRINGER BASEL AG
DOI: 10.1007/s00018-022-04305-2
Keywords
Ca2+ channel; Capacitance measurement; Casein kinase; Endocytosis; FM1-43 imaging; Syndapin; PACSIN
Categories
Funding
- Karolinska Institute
- Berth von Kantzow's Foundation
- Deutsche Forschungsgemeinschaft (DFG) [ERC-2013-AdG 338936-Betalmage]
- European Foundation for the Study of Diabetes
- Family Erling-Persson Foundation
- Skandia Insurance Company, Ltd.
- Stichting af Jochnick Foundation
- Strategic Research Program in Diabetes at Karolinska Institutet
- Swedish Alzheimer Association
- Swedish Diabetes Association
- Swedish Society of Medicine
- Swedish Research Council
- Novo Nordisk Foundation
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Endocytosis is regulated by a complex molecular machinery, in which syndapin I/PACSIN 1 plays a crucial role in pancreatic beta cells by interacting with neural Wiskott-Aldrich syndrome protein (N-WASP) to drive endocytosis.
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 beta cells and that its knockdown abrogates beta cell endocytosis leading to disturbed plasma membrane protein homeostasis, as exemplified by an elevated density of L-type Ca2+ channels. Intriguingly, inositol hexakisphosphate (InsP(6)) 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 beta cell endocytosis. Dominant-negative interference with endogenous syndapin I/PACSIN 1 protein complexes, by overexpression of the syndapin I/PACSIN 1 SH3 domain, decreases InsP(6)-stimulated endocytosis. InsP(6) 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 beta cells.
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