ONCOMODULIN IS EXPRESSED EXCLUSIVELY BY OUTER HAIR-CELLS IN THE ORGANOF CORTI

Oncomodulin (OM) is a small, acidic calcium-binding protein first disc overed in a rat hepatoma and later found in placental cytotrophoblasts , the pre-implantation embryo, and in a wide variety of neoplastic tis sues. OM was considered to be exclusively an oncofetal protein until i ts recent detection in extracts of the adult guinea pig's organ of Cor ti. Here we report that light and electron microscopic immunostaining of gerbil, rat, and mouse inner ears with a monoclonal antibody agains t recombinant rat OM localizes the protein exclusively in cochlear out er hair cells (OHCs). At the ultrastructural revel, high gold labeling density was seen overlying the nucleus, cytoplasm, and the cuticular plate of gerbil OHCs. Few, if any, gold particles were present over in tracellular organelles and the stereocilia. Staining of a wide range o f similarly processed gerbil organs failed to detect immunoreactive OM in any other adult tissues. The mammalian genome encodes one alpha- a nd one beta-isoform of parvalbumin (PV). The widely distributed alpha PV exhibits a Very high affinity for Ca2+ and is believed to serve as a Ca2+ buffer. By contrast, OM, the mammalian beta PV, displays a high ly attenuated affinity for Ca2+, consistent with a Ca2+-dependent regu latory function. The exclusive association of OM with cochlear OHCs in mature tissues is likely to have functional relevance. Teleological c onsiderations favor its involvement in regulating some aspect of OHC e lectromotility. Although the fast electromotile response of OHCs does not require Ca2+, its gain and magnitude are modulated by efferent inn ervation. Therefore, OM may be involved in mediation of intracellular responses to cholinergic stimulation, which are known to be Ca2+ regul ated.