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Cholesterol-Binding Toxins and Anti-cholesterol Antibodies as Structural Probes for Cholesterol Localization

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Cholesterol Binding and Cholesterol Transport Proteins:

Part of the book series: Subcellular Biochemistry ((SCBI,volume 51))

Abstract

Cholesterol is one of the major constituents of mammalian cell membranes. It plays an indispensable role in regulating the structure and function of cell membranes and affects the pathology of various diseases. In recent decades much attention has been paid to the existence of membrane microdomains, generally termed lipid “rafts”, and cholesterol, along with sphingolipids, is thought to play a critical role in raft structural organization and function. Cholesterol-binding probes are likely to provide useful tools for analyzing the distribution and dynamics of membrane cholesterol, as a structural element of raft microdomains, and elsewhere within the cell. Among the probes, non-toxic derivatives of perfringolysin O, a cholesterol-binding cytolysin, bind cholesterol in a concentration-dependent fashion with a strict threshold. They selectively recognize cholesterol in cholesterol-enriched membranes, and have been used in many studies to detect microdomains in plasma and intracellular membranes. Anti-cholesterol antibodies that recognize cholesterol in domain structures have been developed in recent years. In this chapter, we describe the characteristics of these cholesterol-binding proteins and their applications to studies on membrane cholesterol localization.

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Abbreviations

PFO,:

perfringolysin O;

EGFP,:

enhanced green fluorescent protein;

DRMs,:

detergent-resistant membranes;

βCD,:

β-cyclodextrin;

SFKs,:

Src-family protein kinases;

TD,:

Tangier disease;

NPC,:

Niemann-Pick disease type C

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Acknowledgements

Work in the authors’ laboratory is supported in part by Grants-in-Aid for Science Research from the Japan Society for the Promotion of Science (to Y. O.-I. and to M. I.). We thank Dr. M.M. Dooley-Ohto for reading the manuscript.

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Authors and Affiliations

  1. Faculty of Pharmacy, Iwaki Meisei University, 5-5-1 Chuodai Iino, Iwaki City, Fukushima, 970-8551, Japan

    Yoshiko Ohno-Iwashita & Shintaro Iwashita

  2. Research Team for Functional Genomics, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo, 173-0015, Japan

    Yoshiko Ohno-Iwashita, Yukiko Shimada, Masami Hayashi, Machiko Iwamoto & Mitsushi Inomata

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  1. Yoshiko Ohno-Iwashita
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  2. Yukiko Shimada
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  3. Masami Hayashi
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  4. Machiko Iwamoto
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  5. Shintaro Iwashita
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  6. Mitsushi Inomata
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Correspondence to Yoshiko Ohno-Iwashita .

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    J. Robin Harris

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Ohno-Iwashita, Y., Shimada, Y., Hayashi, M., Iwamoto, M., Iwashita, S., Inomata, M. (2010). Cholesterol-Binding Toxins and Anti-cholesterol Antibodies as Structural Probes for Cholesterol Localization. In: Harris, J. (eds) Cholesterol Binding and Cholesterol Transport Proteins:. Subcellular Biochemistry, vol 51. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-8622-8_22

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