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The Journal of Neuroscience, June 15, 1999, 19(12):4815-4827
The Supporting-Cell Antigen: A Receptor-Like Protein Tyrosine Phosphatase Expressed in the Sensory Epithelia of the Avian Inner Ear
Robert P. Kruger1, Richard J. Goodyear1, P. Kevin Legan1, Mark E. Warchol2, Yehoash Raphael3, Douglas A. Cotanche4, and Guy P. Richardson1 1 School of Biological Sciences, The University of Sussex, Falmer, Brighton, BN1 9QG, United Kingdom, 2 Central Institute for the Deaf, St. Louis, Missouri 63110, 3 Kresge Hearing Research Institute, Ann Arbor, Michigan 48109-0648, and 4 Department of Otolaryngology and Communication Disorders, The Children's Hospital, Boston Massachusetts 02115
After noise- or drug-induced hair-cell loss, the sensory epithelia of the avian inner ear can regenerate new hair cells. Few molecular markers are available for the supporting-cell precursors of the hair cells that regenerate, and little is known about the signaling mechanisms underlying this regenerative response. Hybridoma methodology was used to obtain a monoclonal antibody (mAb) that stains the apical surface of supporting cells in the sensory epithelia of the inner ear. The mAb recognizes the supporting-cell antigen (SCA), a protein that is also found on the apical surfaces of retinal Müller cells, renal tubule cells, and intestinal brush border cells. Expression screening and molecular cloning reveal that the SCA is a novel receptor-like protein tyrosine phosphatase (RPTP), sharing similarity with human density-enhanced phosphatase, an RPTP thought to have a role in the density-dependent arrest of cell growth. In response to hair-cell damage induced by noise in vivo or hair-cell loss caused by ototoxic drug treatment in vitro, some supporting cells show a dramatic decrease in SCA expression levels on their apical surface. This decrease occurs before supporting cells are known to first enter S-phase after trauma, indicating that it may be a primary rather than a secondary response to injury. These results indicate that the SCA is a signaling molecule that may influence the potential of nonsensory supporting cells to either proliferate or differentiate into hair cells.
Key words: receptor protein tyrosine phosphatase; inner ear; hair cell; supporting cell; development; regeneration
Copyright © 1999 Society for Neuroscience 0270-6474/99/19124815-13$05.00/0
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