Fluorescently Labeled Proteins as a Tool for Analyzing the Dynamics of Protein Quality Control in Living Cells

• KUBOTA Hiroshi

  Department of Life Science, Faculty of Engineering and Resource Science, Akita University

• KITAMURA Akira

  Department of Molecular Cell Dynamics, Faculty of Advanced Life Science, Hokkaido University

• ITOH Hideaki

  Department of Life Science, Faculty of Engineering and Resource Science, Akita University

• KINJO Masataka

  Department of Molecular Cell Dynamics, Faculty of Advanced Life Science, Hokkaido University

• NAGATA Kazuhiro

  Department of Molecular and Cellular Biology, Institute for Frontier Medical Science, Kyoto University

Abstract

Proteins synthesized in living cells often fail to properly fold, and misfolded proteins are potentially toxic to cells due to the existence of exposed hydrophobic surfaces. For example, misfolded proteins tend to aggregate each other and capture other normal proteins into aggregates. Genetic mutations often cause protein misfolding, and these mutations induce neuronal cell death in neurodegenerative diseases (e.g. Alzheimer's disease, Parkinson's disease, polyglutamine disease and amyotrophic lateral sclerosis). However, how misfolded proteins exert cytotoxicity is poorly understood. In living cells, there are two strategies to prevent the toxicity of misfolded proteins: one is prevention of aggregation by molecular chaperones and the other is degradation by proteases. These two systems coordinately monitor quality of proteins and decide the fate of proteins (e.g., reuse after refolding or destruction by protease digestion). We have used aggregation-prone proteins tagged with green fluorescent proteins and derivatives to analyze the dynamics of cytotoxic misfolded proteins in living cells. We discuss how fluorescently labeled proteins are useful to understand the dynamics of misfolded proteins, particularly for those causing neurodegenerative diseases. We also discuss kinetics of interaction between misfolded proteins and binding proteins like molecular chaperones.

Journal

• International Journal of the Society of Materials Engineering for Resources

  International Journal of the Society of Materials Engineering for Resources 17 (1), 1-4, 2010

  The Society of Materials Engineering for Resources of JAPAN

Keywords

• Fluorescently labeled protein
• live cell imaging
• protein dynamics
• protein quality control

Details

• CRID: 1390282680174822656
• NII Article ID: 110007554333
• NII Book ID: AA1095475X
• DOI: 10.5188/ijsmer.17.1
• COI: 1:CAS:528:DC%2BC3cXmtlSmsrY%3D
• ISSN: 18846629
• ISSN: 13479725
• Text Lang: en
• Data Source:
  • JaLC
  • Crossref
  • CiNii Articles
• Abstract License Flag: Disallowed