Imperial College London
Alternate

DrIsabelleLeclerc

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Visiting Professor
 
 
 
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Contact

 

+44 (0)20 7594 3354i.leclerc

 
 
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Location

 

323ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@unpublished{Carrat:2020:10.1101/2020.03.25.007286,
author = {Carrat, GR and Haythorne, E and Tomas, A and Haataja, L and Müller, A and Arvan, P and Piunti, A and Cheng, K and Huang, M and Pullen, TJ and Georgiadou, E and Stylianides, T and Amirruddin, NS and Salem, V and Distaso, W and Cakebread, A and Heesom, KJ and Lewis, PA and Hodson, DJ and Briant, LJ and Fung, ACH and Sessions, RB and Alpy, F and Kong, APS and Benke, PI and Torta, F and Teo, AKK and Leclerc, I and Solimena, M and Wigley, DB and Rutter, GA},
doi = {10.1101/2020.03.25.007286},
title = {The type 2 diabetes gene product STARD10 is a phosphoinositide binding protein that controls insulin secretory granule biogenesis},
url = {http://dx.doi.org/10.1101/2020.03.25.007286},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - UNPB
AB  - <jats:title>Abstract</jats:title><jats:sec><jats:title>Objective</jats:title><jats:p>Risk alleles for type 2 diabetes at the<jats:italic>STARD10</jats:italic>locus are associated with lowered<jats:italic>STARD10</jats:italic>expression in the β-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 β-cell function, are not understood. The aim of this study was to identify the lipids transported and affected by STARD10 in the β-cell and its effect on proinsulin processing and insulin granule biogenesis and maturation.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We used isolated islets from mice deleted selectively in the β-cell for<jats:italic>Stard10</jats:italic>(β<jats:italic>StarD10</jats:italic>KO) and performed electron microscopy, pulse-chase, RNA sequencing and lipidomic analyses. Proteomic analysis of STARD10 binding partners was executed in INS1 (832/13) cell line. X-ray crystallography followed by molecular docking and lipid overlay assay were performed on purified STARD10 protein.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>β<jats:italic>StarD10</jats:italic>KO 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. Amongst the differentially expressed genes in β<jats:italic>StarD10</jats:italic>KO islets, expression of the phosphoinositide binding proteins<jats:italic>Pirt</jats:italic>and<jats:italic>Synaptotagmin 1</jats:
AU  - Carrat,GR
AU  - Haythorne,E
AU  - Tomas,A
AU  - Haataja,L
AU  - Müller,A
AU  - Arvan,P
AU  - Piunti,A
AU  - Cheng,K
AU  - Huang,M
AU  - Pullen,TJ
AU  - Georgiadou,E
AU  - Stylianides,T
AU  - Amirruddin,NS
AU  - Salem,V
AU  - Distaso,W
AU  - Cakebread,A
AU  - Heesom,KJ
AU  - Lewis,PA
AU  - Hodson,DJ
AU  - Briant,LJ
AU  - Fung,ACH
AU  - Sessions,RB
AU  - Alpy,F
AU  - Kong,APS
AU  - Benke,PI
AU  - Torta,F
AU  - Teo,AKK
AU  - Leclerc,I
AU  - Solimena,M
AU  - Wigley,DB
AU  - Rutter,GA
DO  - 10.1101/2020.03.25.007286
PY  - 2020///
TI  - The type 2 diabetes gene product STARD10 is a phosphoinositide binding protein that controls insulin secretory granule biogenesis
UR  - http://dx.doi.org/10.1101/2020.03.25.007286
ER  -
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