University of Oulu

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

Saved in:
Author: Myllymäki, Satu-Marja1; Kämäräinen, Ulla-Reetta1; Liu, Xiaonan2;
Organizations: 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
Format: article
Version: accepted version
Access: open
Online Access: PDF Full Text (PDF, 16.8 MB)
Persistent link:
Language: English
Published: American Society for Biochemistry and Molecular Biology, 2019
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.

see all

Series: Molecular & cellular proteomics
ISSN: 1535-9476
ISSN-E: 1535-9484
ISSN-L: 1535-9476
Volume: 18
Issue: 2
Pages: 277 - 293
DOI: 10.1074/mcp.RA118.001095
Type of Publication: A1 Journal article – refereed
Field of Science: 1182 Biochemistry, cell and molecular biology
Funding: This work was funded by Academy of Finland (251314, 135560, 263770, and 140974 /AM).
Academy of Finland Grant Number: 251314
Detailed Information: 251314 (Academy of Finland Funding decision)
135560 (Academy of Finland Funding decision)
263770 (Academy of Finland Funding decision)
140974 (Academy of Finland Funding decision)
Dataset Reference: Supplemental data:
Copyright information: 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.