A type 2 diabetes disease module with a high collective influence for Cdk2 and PTPLAD1 is localized in endosomes

Boutchueng-Djidjou, M., Belleau, P., Bilodeau, N., Fortier, S., Bourassa, S., Droit, A., Elowe, S., Faure, R. L. (October 2018) A type 2 diabetes disease module with a high collective influence for Cdk2 and PTPLAD1 is localized in endosomes. PLoS One, 13 (10). e0205180. ISSN 1932-6203

[img]
Preview
PDF
2018.Boutchueng.Diabetes.pdf

Download (11Mb) | Preview
URL: https://www.ncbi.nlm.nih.gov/pubmed/30300385
DOI: 10.1371/journal.pone.0205180

Abstract

Despite the identification of many susceptibility genes our knowledge of the underlying mechanisms responsible for complex disease remains limited. Here, we identified a type 2 diabetes disease module in endosomes, and validate it for functional relevance on selected nodes. Using hepatic Golgi/endosomes fractions, we established a proteome of insulin receptor-containing endosomes that allowed the study of physical protein interaction networks on a type 2 diabetes background. The resulting collated network is formed by 313 nodes and 1147 edges with a topology organized around a few major hubs with Cdk2 displaying the highest collective influence. Overall, 88% of the nodes are associated with the type 2 diabetes genetic risk, including 101 new candidates. The Type 2 diabetes module is enriched with cytoskeleton and luminal acidification-dependent processes that are shared with secretion-related mechanisms. We identified new signaling pathways driven by Cdk2 and PTPLAD1 whose expression affects the association of the insulin receptor with TUBA, TUBB, the actin component ACTB and the endosomal sorting markers Rab5c and Rab11a. Therefore, the interactome of internalized insulin receptors reveals the presence of a type 2 diabetes disease module enriched in new layers of feedback loops required for insulin signaling, clearance and islet biology.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > kinase > CDK
diseases & disorders > nutritional and metabolic diseases > diabetes
organs, tissues, organelles, cell types and functions > organs types and functions > liver
CSHL Authors:
Communities: CSHL labs > Krasnitz lab
Depositing User: Matthew Dunn
Date: 9 October 2018
Date Deposited: 01 Nov 2018 19:45
Last Modified: 01 Nov 2018 19:45
PMCID: PMC6177195
Related URLs:
URI: http://repository.cshl.edu/id/eprint/37272

Actions (login required)

Administrator's edit/view item Administrator's edit/view item
CSHL HomeAbout CSHLResearchEducationNews & FeaturesCampus & Public EventsCareersGiving