Oncomodulin is expressed exclusively by outer hair cells in the organ of Corti.
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)
Sakaguchi
N
N
Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
Henzl
M T
MT
Thalmann
I
I
Thalmann
R
R
Schulte
B A
BA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000096:biosynthesis* / Q000276:immunology; D005260:Female; D005849:Gerbillinae; D018072:Hair Cells, Auditory, Outer / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016253:Microscopy, Immunoelectron; D009928:Organ Specificity; D009925:Organ of Corti / Q000166:cytology / Q000378:metabolism*; D016612:Paraffin Embedding; D010320:Parvalbumins / Q000096:biosynthesis; D020033:Protein Isoforms / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley
D000911:Antibodies, Monoclonal; D002135:Calcium-Binding Proteins; D010320:Parvalbumins; D020033:Protein Isoforms; C034733:oncomodulin