Oncomodulin Is Expressed Exclusively by Outer Hair Cells in the Organ of Corti

Abstract

Oncomodulin (OM) is a small, acidic calcium-binding protein first discovered in a rat hepatoma and later found in placental cytotrophoblasts, the pre-implantation embryo, and in a wide variety of neoplastic tissues. OM was considered to be exclusively an oncofetal protein until its recent detection in extracts of the adult guinea pig's organ of Corti. Here we report that light and electron microscopic immunostaining of gerbil, rat, and mouse inner ears with a monoclonal antibody against recombinant rat OM localizes the protein exclusively in cochlear outer hair cells (OHCs). At the ultrastructural level, 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 intracellular organelles and the stereocilia. Staining of a wide range of similarly processed gerbil organs failed to detect immunoreactive OM in any other adult tissues. The mammalian genome encodes one alpha- and 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 highly attenuated affinity for Ca2+, consistent with a Ca2+-dependent regulatory function. The exclusive association of OM with cochlear OHCs in mature tissues is likely to have functional relevance. Teleological considerations favor its involvement in regulating some aspect of OHC electromotility. Although the fast electromotile response of OHCs does not require Ca2+, its gain and magnitude are modulated by efferent innervation. Therefore, OM may be involved in mediation of intracellular responses to cholinergic stimulation, which are known to be Ca2+ regulated. (J Histochem Cytochem 46:29-39, 1998)

Upregulated expression of oncomodulin, the beta isoform of parvalbumin, in perikarya and axons in the diencephalon of parvalbumin knockout mice

“…OM, the beta isoform of parvalbumin, discovered by MacManus (1979) and by Brewer and MacManus (1987) was known until now to be present in adult mammals only in the organ of Corti of the inner ear, in particular in the outer hair cells (Thalmann et al, 1995;Sakaguchi et al, 1998, Hackney et al, 2005. According to our present studies, an extensive system of OM-immunoreactive axons is present in the diencephalon of PV-deficient animals.…”

Microscale analysis of proteins in inner ear tissues and fluids with emphasis on endolymphatic sac, otoconia, and organ of Corti

“…By first subdividing the organ of Corti into inner and outer layers, and ultimately into individual cell layers (Fig. 1C) we were able to localize oncomodulin expression exclusively to the outer hair cells later confirmed by immunohistochemistry [34]. Using the same techniques we were able to quantify the protein in the outer hair cells [35].…”

Cytosolic Ca2+ Buffers

“…OM is present in the organ of Corti (Thalmann et al 1995), more precisely in cochlear outer hair cells (Sakaguchi et al 1998) in gerbil, rat, and mouse. An extracellular role for OM in retinal ganglion cell regeneration (Yin et al 2006) was reported, but see also Hauk et al (2008) and Schwaller (2009).…”