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

doi:10.1007/s00018-022-04305-2

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

School of Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

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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 language	English
Article number	286
Number of pages	17
Journal	Cellular and Molecular Life Sciences
Volume	79
Issue number	6
Early online date	9 May 2022
DOIs	https://doi.org/10.1007/s00018-022-04305-2
Publication status	Published online - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1007/s00018-022-04305-2

Shi2022_Article_InositolHexakisphosphatePrimesFinal published version, 5.49 MBLicence: CC BY

Cite this

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title = "Inositol hexakisphosphate primes syndapin I/PACSIN 1 activation in endocytosis",

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.",

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author = "Yue Shi and Kaixuan Zhao and Guang Yang and Jia Yu and Yuxin Li and Kessels, {Michael M} and Lina Yu and Britta Qualmann and Per-Olof Berggren and Shao-Nian Yang",

note = "Funding Information: Open access funding provided by Karolinska Institute. This work was supported by grants from Berth von Kantzow{\textquoteright}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: {\textcopyright} 2022, The Author(s).",

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AU - Shi, Yue

AU - Zhao, Kaixuan

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AU - Yu, Jia

AU - Li, Yuxin

AU - Kessels, Michael M

AU - Yu, Lina

AU - Qualmann, Britta

AU - Berggren, Per-Olof

AU - Yang, Shao-Nian

N1 - 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).

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N2 - 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.

AB - 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.

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DO - 10.1007/s00018-022-04305-2

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SN - 1420-682X

VL - 79

JO - Cellular and Molecular Life Sciences

JF - Cellular and Molecular Life Sciences

IS - 6

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ER -

Inositol hexakisphosphate primes syndapin I/PACSIN 1 activation in endocytosis

Abstract

Bibliographical note

Keywords

UN SDGs

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