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The Journal of Neuroscience, February 1, 2001, 21(3):849-857

ATP-Binding Cassette Transporter ABC2/ABCA2 in the Rat Brain: A Novel Mammalian Lysosome-Associated Membrane Protein and a Specific Marker for Oligodendrocytes But Not for Myelin Sheaths

Cheng-Ji Zhou^{1, 4}, Li-Xia Zhao², Nobuya Inagaki^{2, 5}, Jian-Lian Guan¹, Shigeo Nakajo³, Takahiro Hirabayashi³, Sakae Kikuyama⁴, and Seiji Shioda^{1, 5}

¹ Department of Anatomy, Showa University School of Medicine, Tokyo, 142-8555 Japan, ² Department of Physiology, Akita University School of Medicine, Akita, 010-8543 Japan, ³ Laboratory of Biological Chemistry, Showa University School of Pharmaceutical Sciences, Tokyo, 142-8555 Japan, ⁴ Department of Biology, Waseda University School of Education, Tokyo, 168-8050 Japan, and ⁵  Department of Anatomy I, Showa University School of Medicine, Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555 Japan

We recently cloned a full-length cDNA of the rat ATP-binding cassette transporter 2 (ABC2, or ABCA2) protein, a member of the ABC1 (or ABCA) subfamily (-ABC1/ABCA1 is a causal gene for Tangier disease) and found it to be strongly expressed in the rat brain. In this study, we identified ABC2 as a lysosome-associated membrane protein that is being localized specifically in oligodendrocytes. The ABC2-immunolabeled cells were detected mainly in the white matter but were also scattered in gray matter throughout the whole brain. In addition, these cells were found to be colocalized with 2',3'-cyclic nucleotide-3'-phosphodiesterase (CNPase) immunoreactivity when the marker antibody for oligodendrocytes was used. However, no such colocalization was observed with markers for other kinds of glial cells. Unlike the CNP antibody, which also intensely stains myelin sheaths in the white matter, ABC2 immunoreactivity was detected only in the cell bodies of oligodendrocytes. At the ultrastructural level, ABC2 immunoreactivity was detected mostly around lysosome and partly in Golgi apparatus by electron microscopy. This was confirmed by immunocolocalization of ABC2 and lysosomal markers in a neuroblastoma cell line. Immunoblotting analysis of ABC2 from the whole brain and the ABC2-transfected cell line revealed bands at ~260 kDa. The result of in situ hybridization with a riboprobe for ABC2 matched the results obtained from immunostaining. These findings strongly suggest that ABC2 is a specific marker for oligodendrocytes but not for myelinsheaths and that it is as a novel mammalian lysosome-associated membrane protein involved in myelinization or other kinds of metabolism in the CNS.

Key words: ATP-binding cassette (ABC) transporter; ABC1 (or ABCA) subfamily; ABC2/ABCA2; oligodendrocytes; myelinization; lysosomes; marker protein; CNPase; lysosome-associated membrane protein LAMP1/LAMP2; rat brain

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Copyright © 2001 Society for Neuroscience  0270-6474/01/213849-09$05.00/0

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