Microscopic image-based covariation network analysis for actin scaffold-modified insulin signaling

Yoshiyuki Noguchi; Fumi Kano; Nobuhiko Maiya; Chisako Iwamoto; Shoko Yamasaki; Yosuke Otsubo; Daiki Nakatsu; Rina Kunishige; Masayuki Murata

doi:10.1016/j.isci.2021.102724

Microscopic image-based covariation network analysis for actin scaffold-modified insulin signaling

iScience. 2021 Jul 13;24(7):102724. doi: 10.1016/j.isci.2021.102724. eCollection 2021 Jul 23.

Authors

Yoshiyuki Noguchi¹, Fumi Kano², Nobuhiko Maiya³, Chisako Iwamoto³, Shoko Yamasaki⁴, Yosuke Otsubo⁴, Daiki Nakatsu², Rina Kunishige^{1

2}, Masayuki Murata^{1

2}

Affiliations

¹ Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo 153-8902, Japan.
² Cell Biology Center, Institute of Innovative Research, Tokyo Institute of Technology, 4259 Nagatsuta, Midori-ku, Yokohama, Kanagawa 226-8503, Japan.
³ System Development Department, Technology Solutions Sector, Healthcare Business Unit, NIKON CORPORATION, 471, Nagaodai-cho, Sakae-ku, Yokohama, Kanagawa 244-8533, Japan.
⁴ Mathematical Sciences Research Laboratory, Research & Development Division, NIKON CORPORATION, 471, Nagaodai-cho, Sakae-ku, Yokohama, Kanagawa 244-8533, Japan.

Abstract

To infer a "live" protein network in single cells, we developed a novel Protein Localization and Modification-based Covariation Network (PLOM-CON) analysis method using a large set of quantitative data on the abundance (quantity), post-translational modification state (quality), and localization/morphological information of target proteins from microscope immunostained images. The generated network exhibited synchronized time-dependent behaviors of the target proteins to visualize how a live protein network develops or changes in cells under specific experimental conditions. As a proof of concept for PLOM-CON analysis, we applied this method to elucidate the role of actin scaffolds, in which actin fibers and signaling molecules accumulate and form membrane-associated protein condensates, in insulin signaling in rat hepatoma cells. We found that the actin scaffold in cells may function as a platform for glycogenesis and protein synthesis upon insulin stimulation.

Keywords: Bioinformatics; Molecular network; Systems biology.