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

Chengji Zhou, Li Xia Zhao, Nobuya Inagaki, Jian Lian Guan, Shigeo Nakajo, Takahiro Hirabayashi, Sakae Kikuyama, Seiji Shioda

Research output: Contribution to journalArticle

62 Scopus citations

Abstract

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 lysosomeassociated 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.

Original languageEnglish (US)
Pages (from-to)849-857
Number of pages9
JournalJournal of Neuroscience
Volume21
Issue number3
StatePublished - 2001
Externally publishedYes

Keywords

  • ABC1 (or ABCA) subfamily
  • ABC2/ABCA2
  • ATP-binding cassette (ABC) transporter
  • CNPase
  • Lysosome-associated membrane protein LAMP1/LAMP2
  • Lysosomes
  • Marker protein
  • Myelinization
  • Oligodendrocytes
  • Rat brain

ASJC Scopus subject areas

  • Neuroscience(all)

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