The type 2 diabetes gene product STARD10 is a phosphoinositide-binding protein that controls insulin secretory granule biogenesis

被引：18

作者：

Carrat, Gaelle R. ^{[1
]}

Haythorne, Elizabeth ^{[1
]}

Tomas, Alejandra ^{[1
]}

Haataja, Leena ^{[2
]}

Mueller, Andreas ^{[3
,4
,5
,6
,7
,8
]}

Arvan, Peter ^{[2
]}

Piunti, Alexandra ^{[1
,9
]}

Cheng, Kaiying ^{[10
]}

Huang, Mutian ^{[1
]}

Pullen, Timothy J. ^{[1
,11
]}

Georgiadou, Eleni ^{[1
]}

Stylianides, Theodoros ^{[12
]}

Amirruddin, Nur Shabrina ^{[13
,14
]}

Salem, Victoria ^{[1
,15
]}

Distaso, Walter ^{[16
]}

Cakebread, Andrew ^{[17
]}

Heesom, Kate J. ^{[18
]}

Lewis, Philip A. ^{[18
]}

Hodson, David J. ^{[19
,20
,21
,22
]}

Briant, Linford J. ^{[23
]}

Fung, Annie C. H. ^{[24
]}

Sessions, Richard B. ^{[25
]}

Alpy, Fabien ^{[26
]}

Kong, Alice P. S. ^{[24
]}

Benke, Peter, I ^{[27
]}

Torta, Federico ^{[27
]}

Teo, Adrian Kee Keong ^{[13
,14
,28
]}

Leclerc, Isabelle ^{[1
]}

Solimena, Michele ^{[3
,4
,5
,6
,7
,8
]}

Wigley, Dale B. ^{[10
]}

Rutter, Guy A. ^{[1
]}

机构：

[1] Imperial Coll London, Sect Cell Biol & Funct Genom, du Cane Rd, London W12 ONN, England

[2] Univ Michigan, Med Sch, Div Metab Endocrinol & Diabet, Dept Internal Med, Ann Arbor, MI 48109 USA

[3] Tech Univ Dresden, Univ Hosp, Mol Diabetol, Dresden, Germany

[4] Tech Univ Dresden, Fac Med Carl Gustav Carus, Dresden, Germany

[5] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Helmholtz Ctr Munich, Paul Langerhans Inst Dresden PLID, Dresden, Germany

[6] Tech Univ Dresden, Fac Med, Dresden, Germany

[7] German Ctr Diabet Res DZD eV, Neuherberg, Germany

[8] Max Planck Inst Mol Cell Biol & Genet MPI CBG, Dresden, Germany

[9] Lille 1 Univ, Sci & Technol, F-59655 Villeneuve Dascq, France

[10] Imperial Coll London, Dept Med, Sect Struct Biol, London, England

[11] Kings Coll London, Fac Life Sci & Med, Dept Diabet, London, England

[12] Loughborough Univ, Ctr Innovat & Collaborat Construct Engn, Loughborough LE11 3TU, Leics, England

[13] ASTAR, Inst Mol & Cell Biol IMCB, Stem Cells & Diabet Lab, Singapore 138673, Singapore

[14] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Med, Singapore 119228, Singapore

[15] Imperial Coll London, Dept Med, Sect Invest Med, du Cane Rd, London W12 ONN, England

[16] Imperial Coll London, Imperial Coll Business Sch, Exhibit Rd, London SW7 2AZ, England

[17] Kings Coll London, London Metall Facil, London WC2R 2LS, England

[18] Univ Bristol, Prote Facil, Bristol, Avon, England

[19] Birmingham Hlth Partners, Ctr Endocrinol Diabet & Metab, Birmingham, W Midlands, England

[20] Univ Birmingham, Inst Metab & Syst Res, Edgbaston, England

[21] Univ Birmingham, Ctr Membrane Prot & Receptors, Midlands, England

[22] Univ Nottingham, Midlands, England

[23] Univ Oxford, Churchill Hosp, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7LE, England

[24] Chinese Univ Hong Kong, Dept Med & Therapeut, Shatin, Hong Kong, Peoples R China

[25] Univ Bristol, Fac Life Sci, Sch Biochem, Bristol BS8 1TD, Avon, England

[26] Univ Strasbourg, Inst Genet & Biol Mol & Cellulaire IGBMC, INSERM, UMR 7104,U1258,CNRS, 1 Rue Laurent Fries, F-67404 Illkirch Graffenstaden, France

[27] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Biochem, Singapore Lipid Incubator, 8 Mdical Dr, Singapore 117596, Singapore

[28] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Biochem, Singapore 117596, Singapore

来源：

MOLECULAR METABOLISM | 2020年 / 40卷

基金：

英国惠康基金; 英国生物技术与生命科学研究理事会; 英国医学研究理事会; 欧洲研究理事会; 欧盟地平线“2020”;

关键词：

Type; 2; diabetes; Pancreatic beta-cell; Lipid transporter; Insulin granule biogenesis; Phosphoinositides; PANCREATIC BETA-CELLS; GLUCOSE-HOMEOSTASIS; CHOLESTEROL; ISLETS; GRANUPHILIN; ASSOCIATION; DISRUPTION; ACTIVATION; EXOCYTOSIS; EXPRESSION;

D O I：

10.1016/j.molmet.2020.101015

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objective: Risk alleles for type 2 diabetes at the STARD10 locus are associated with lowered STARD10 expression in the beta-cell, impaired glucose-induced insulin secretion, and decreased circulating proinsulin:insulin ratios. Although likely to serve as a mediator of intracellular lipid transfer, the identity of the transported lipids and thus the pathways through which STARD10 regulates beta-cell function are not understood. The aim of this study was to identify the lipids transported and affected by STARD10 in the beta-cell and the role of the protein in controlling proinsulin processing and insulin granule biogenesis and maturation. Metkods: We used isolated islets from mice deleted selectively in the beta-cell for Stard10 (beta Stard10KO) and performed electron microscopy, pulse-chase, RNA sequencing, and lipidomic analyses. Proteomic analysis of STARD10 binding partners was executed in the INS1 (832/13) cell line. X-ray crystallography followed by molecular docking and lipid overlay assay was performed on purified STARD10 protein. Results: beta Stard10KO islets had a sharply altered dense core granule appearance, with a dramatic increase in the number of "rod-like" dense cores. Correspondingly, basal secretion of proinsulin was increased versus wild-type islets. The solution of the crystal structure of STARD10 to 2.3 angstrom resolution revealed a binding pocket capable of accommodating polyphosphoinositides, and STARD10 was shown to bind to inositides phosphorylated at the 3' position. Lipidomic analysis of beta Stard10KO islets demonstrated changes in phosphatidylinositol levels, and the inositol lipid kinase PIP4K2C was identified as a STARD10 binding partner. Also consistent with roles for STARD10 in phosphoinositide signalling, the phosphoinositide-binding proteins Pirt and Synaptotagmin 1 were amongst the differentially expressed genes in beta Stard10KO islets. Conclusion: Our data indicate that STARD10 binds to, and may transport, phosphatidylinositides, influencing membrane lipid composition, insulin granule biosynthesis, and insulin processing. (C) 2020 The Authors. Published by Elsevier GmbH.

引用

页数：16

共 80 条

[1] Complexin I regulates glucose-induced secretion in pancreatic β-cells [J].

Abderrahmani, A ;

Niederhauser, G ;

Plaisance, V ;

Roehrich, ME ;

Lenain, V ;

Coppola, T ;

Regazzi, R ;

Waeber, G .

JOURNAL OF CELL SCIENCE, 2004, 117 (11) :2239-2247

[2] PHENIX: a comprehensive Python']Python-based system for macromolecular structure solution [J].

Adams, Paul D. ;

Afonine, Pavel V. ;

Bunkoczi, Gabor ;

Chen, Vincent B. ;

Davis, Ian W. ;

Echols, Nathaniel ;

Headd, Jeffrey J. ;

Hung, Li-Wei ;

Kapral, Gary J. ;

Grosse-Kunstleve, Ralf W. ;

McCoy, Airlie J. ;

Moriarty, Nigel W. ;

Oeffner, Robert ;

Read, Randy J. ;

Richardson, David C. ;

Richardson, Jane S. ;

Terwilliger, Thomas C. ;

Zwart, Peter H. .

ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, 2010, 66 :213-221

[3]

ARVAN P, 1991, J BIOL CHEM, V266, P14171

[4] Sorting ourselves out: Seeking consensus on trafficking in the beta-cell [J].

Arvan, P ;

Halban, PA .

TRAFFIC, 2004, 5 (01) :53-61

[5] Two SUR1-specific histidine residues mandatory for zinc-induced activation of the rat KATP channel [J].

Bancila, V ;

Cens, T ;

Monnier, D ;

Chanson, F ;

Faure, C ;

Dunant, Y ;

Bloc, A .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (10) :8793-8799

[6] Cholesterol Accumulation Increases Insulin Granule Size and Impairs Membrane Trafficking [J].

Bogan, Jonathan S. ;

Xu, Yingke ;

Hao, Mingming .

TRAFFIC, 2012, 13 (11) :1466-1480

[7] Impaired Islet Function in Commonly Used Transgenic Mouse Lines due to Human Growth Hormone Minigene Expression [J].

Brouwers, Bas ;

de Faudeur, Geoffroy ;

Osipovich, Anna B. ;

Goyvaerts, Lotte ;

Lemaire, Katleen ;

Boesmans, Leen ;

Cauwelier, Elisa J. G. ;

Granvik, Mikaela ;

Pruniau, Vincent P. E. G. ;

Van Lommel, Leentje ;

Van Schoors, Jolien ;

Stancill, Jennifer S. ;

Smolders, Ilse ;

Goffin, Vincent ;

Binart, Nadine ;

in't Veld, Peter ;

Declercq, Jeroen ;

Magnuson, Mark A. ;

Creemers, John W. M. ;

Schuit, Frans ;

Schraenen, Anica .

CELL METABOLISM, 2014, 20 (06) :979-990

[8] β-cell ABCA1 influences insulin secretion, glucose homeostasis and response to thiazolidinedione treatment [J].

Brunham, Liam R. ;

Kruit, Janine K. ;

Pape, Terry D. ;

Timmins, Jenelle M. ;

Reuwer, Anne Q. ;

Vasanji, Zainisha ;

Marsh, Brad J. ;

Rodrigues, Brian ;

Johnson, James D. ;

Parks, John S. ;

Verchere, C. Bruce ;

Hayden, Michael R. .

NATURE MEDICINE, 2007, 13 (03) :340-347

[9] Decreased STARD10 Expression Is Associated with Defective Insulin Secretion in Humans and Mice [J].

Carrat, Gaelle R. ;

Hu, Ming ;

Nguyen-Tu, Marie-Sophie ;

Chabosseau, Pauline ;

Gaulton, Kyle J. ;

van de Bunt, Martijn ;

Siddiq, Afshan ;

Falchi, Mario ;

Thurner, Matthias ;

Canouil, Mickael ;

Pattou, Francois ;

Leclerc, Isabelle ;

Pullen, Timothy J. ;

Cane, Matthew C. ;

Prabhala, Priyanka ;

Greenwald, William ;

Schulte, Anke ;

Marchetti, Piero ;

Ibberson, Mark ;

MacDonald, Patrick E. ;

Fox, Jocelyn E. Manning ;

Gloyn, Anna L. ;

Froguel, Philippe ;

Solimena, Michele ;

McCarthy, Mark I. ;

Rutter, Guy A. .

AMERICAN JOURNAL OF HUMAN GENETICS, 2017, 100 (02) :238-256

[10] Mitochondrial and ER-Targeted eCALWY Probes Reveal High Levels of Free Zn2+ [J].

Chabosseau, Pauline ;

Tuncay, Erkan ;

Meur, Gargi ;

Bellomo, Elisa A. ;

Hessels, Anne ;

Hughes, Stephen ;

Johnson, Paul R. V. ;

Bugliani, Marco ;

Marchetti, Piero ;

Turan, Belma ;

Lyon, Alexander R. ;

Merkx, Maarten ;

Rutter, Guy A. .

ACS CHEMICAL BIOLOGY, 2014, 9 (09) :2111-2120

← 1 2 3 4 5 6 7 8 →