A comparative analysis of paxillin and Hic‐5 proximity interactomes

Author:

Brock Katia1,Alpha Kyle M.1,Brennan Grant1,De Jong Ebbing P.2,Luke Elizabeth1,Turner Christopher E.1ORCID

Affiliation:

1. Department of Cell and Developmental Biology State University of New York Upstate Medical University Syracuse New York USA

2. Proteomics Core Facility State University of New York Upstate Medical University Syracuse New York USA

Abstract

AbstractFocal adhesions serve as structural and signaling hubs, facilitating bidirectional communication at the cell–extracellular matrix interface. Paxillin and the related Hic‐5 (TGFβ1i1) are adaptor/scaffold proteins that recruit numerous structural and regulatory proteins to focal adhesions, where they perform both overlapping and discrete functions. In this study, paxillin and Hic‐5 were expressed in U2OS osteosarcoma cells as biotin ligase (BioID2) fusion proteins and used as bait proteins for proximity‐dependent biotinylation in order to directly compare their respective interactomes. The fusion proteins localized to both focal adhesions and the centrosome, resulting in biotinylation of components of each of these structures. Biotinylated proteins were purified and analyzed by mass spectrometry. The list of proximity interactors for paxillin and Hic‐5 comprised numerous shared core focal adhesion proteins that likely contribute to their similar functions in cell adhesion and migration, as well as proteins unique to paxillin and Hic‐5 that have been previously localized to focal adhesions, the centrosome, or the nucleus. Western blotting confirmed biotinylation and enrichment of FAK and vinculin, known interactors of Hic‐5 and paxillin, as well as several potentially unique proximity interactors of Hic‐5 and paxillin, including septin 7 and ponsin, respectively. Further investigation into the functional relationship between the unique interactors and Hic‐5 or paxillin may yield novel insights into their distinct roles in cell migration.

Funder

National Institutes of Health

Publisher

Wiley

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