Myllymäki, S., Ulla-Reetta, K., Xiaonan, L., Pereira, C., Sini, M., Mikko, V., Markku, V., Aki, M. (2018) Assembly of the β4-Integrin Interactome Based on Proximal Biotinylation in the Presence and Absence of Heterodimerization. Molecular and Cellular Proteomics, 18 (2), 277-293. doi:10.1074/mcp.RA118.001095
Assembly of the β4-integrin interactome based on proximal biotinylation in the presence and absence of heterodimerization
|Author:||Myllymäki, Satu-Marja1; Kämäräinen, Ulla-Reetta1; Liu, Xiaonan2;|
1Oulu Center for Cell-Matrix Research, Biocenter Oulu, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Finland
2Institute of Biotechnology and Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland
|Online Access:||PDF Full Text (PDF, 16.8 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe201902134732
American Society for Biochemistry and Molecular Biology,
|Publish Date:|| 2019-02-13
Integrin-mediated laminin adhesions mediate epithelial cell anchorage to basement membranes and are critical regulators of epithelial cell polarity. Integrins assemble large multiprotein complexes that link to the cytoskeleton and convey signals into the cells. Comprehensive proteomic analyses of actin network-linked focal adhesions (FA) have been performed, but the molecular composition of intermediate filament-linked hemidesmosomes (HD) remains incompletely characterized. Here we have used proximity-dependent biotin identification (BioID) technology to label and characterize the interactome of epithelia-specific β4-integrin that, as α6β4-heterodimer, forms the core of HDs. The analysis identified ∼150 proteins that were specifically labeled by BirA-tagged integrin-β4. In addition to known HDs proteins, the interactome revealed proteins that may indirectly link integrin-β4 to actin-connected protein complexes, such as FAs and dystrophin/dystroglycan complexes. The specificity of the screening approach was validated by confirming the HD localization of two candidate β4-interacting proteins, utrophin (UTRN) and ELKS/Rab6-interacting/CAST family member 1 (ERC1). Interestingly, although establishment of functional HDs depends on the formation of α6β4-heterodimers, the assembly of β4-interactome was not strictly dependent on α6-integrin expression. Our survey to the HD interactome sets a precedent for future studies and provides novel insight into the mechanisms of HD assembly and function of the β4-integrin.
Molecular & cellular proteomics
|Pages:||277 - 293|
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
1182 Biochemistry, cell and molecular biology
This work was funded by Academy of Finland (251314, 135560, 263770, and 140974 /AM).
|Academy of Finland Grant Number:||
251314 (Academy of Finland Funding decision)
135560 (Academy of Finland Funding decision)
263770 (Academy of Finland Funding decision)
140974 (Academy of Finland Funding decision)
This research was originally published in Molecular & Cellular Proteomics. Myllymäki, S.-M., Kämäräinen, U.-R., Liu, X., Cruz, S. P., Miettinen, S., Vuorela, M., Varjosalo, M., Manninen, A. Assembly of the β4-integrin interactome based on proximal biotinylation in the presence and absence of heterodimerization. Mol Cell Proteomics. 2019; 18 (2): 277-293. © Myllymäki et al.