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The Journal of Neuroscience, February 18, 2004, 24(7):1772-1779; doi:10.1523/JNEUROSCI.5063-03.2004

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Cellular/Molecular
Identification and Characterization of Choline Transporter-Like Protein 2, an Inner Ear Glycoprotein of 68 and 72 kDa That Is the Target of Antibody-Induced Hearing Loss

Thankam S. Nair, Kelley E. Kozma, Nickoleta L. Hoefling, Pavan K. Kommareddi, Yo Ueda, Tzy-Wen Gong, Margaret I. Lomax, Christopher D. Lansford, Steven A. Telian, Bulent Satar, H. Alexander Arts, Hussam K. El-Kashlan, Wayne E. Berryhill, Yehoash Raphael, and Thomas E. Carey

Department of Otolaryngology/Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan 48109-0506

The Kresge Hearing Research Institute-3 (KHRI-3) antibody binds to a guinea pig inner ear supporting cell antigen (IESCA) and causes hearing loss. To gain insight into the mechanism of antibody-induced hearing loss, we used antibody immunoaffinity purification to isolate the IESCA, which was then sequenced by mass spectroscopy, revealing 10 guinea pig peptides identical to sequences in human choline transporter-like protein 2 (CTL2). Full-length CTL2 cDNA sequenced from guinea pig inner ear has 85.9% identity with the human cDNA. Consistent with its expression on the surface of supporting cells in the inner ear, CTL2 contains 10 predicted membrane-spanning regions with multiple N-glycosylation sites. The 68 and 72 kDa molecular forms of inner ear CTL2 are distinguished by sialic acid modification of the carbohydrate. The KHRI-3 antibody binds to an N-linked carbohydrate on CTL2 and presumably damages the organ of Corti by blocking the transporter function of this molecule. CTL2 mRNA and protein are abundantly expressed in human inner ear. Sera from patients with autoimmune hearing loss bind to guinea pig inner ear with the same pattern as CTL2 antibodies. Thus, CTL2 is a possible target of autoimmune hearing loss in humans.

Key words: antibody; antigen; auditory; autoimmunity; cochlea; deafness; choline; membrane; transport

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Received Nov 14, 2003; revised December 17, 2003; accepted December 17, 2003.

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