title: Soluble megalin is accumulated in the lumen of the rat endolymphatic sac.
abstract: The endolymphatic sac (ES) is believed to play an important role in maintaining homeostasis in the inner ear by the absorption and endocytosis of endolymph. Megalin is a 600-kDa multiligand endocytic receptor expressed in certain types of absorptive epithelia including kidney proximal tubules. We analyzed the immunoreactivity for megalin in rat ES by immunofluorescence, immunogold electron microscopy, and immunoblotting. With immunostaining, the luminal substances of the ES were strongly stained for megalin. Megalin was also localized in luminal macrophage-like cells and both types of epithelial cell (mitochondria-rich cells and ribosome-rich cells). In these cells, the megalin was localized in the lumen of endosomes, but was not membrane associated. This localization pattern indicates that the megalin in these cells is not a membrane receptor, but merely one of the constituents that are endocytosed from the lumen of the ES. Immunoblotting indicated that the megalin in the ES is a 210-kDa molecule lacking a cytoplasmic domain. This suggests that the megalin in the ES may be a soluble form, different from the 600-kDa membrane-bound receptor expressed in kidneys. Taken together, it is likely that the megalin in the ES lumen is a soluble component and may be endocytosed by the ES epithelial cells. Furthermore, we found that the tectorial membrane, an acellular structure in the cochlea, gave a strong megalin immunoreaction. Since the cochlea is connected to the ES, the megalin may be transported alone or with the components of the tectorial membrane from the cochlea to the ES lumen through longitudinal flow.
authors.affiliation: Department of Histology and Cell Biology, School of Medicine, Kagawa University, Miki, Kagawa 761-0793, Japan. ishidat@kms.ac.jp
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ishida
authors.forename: Tanenori
authors.initials: T
authors.lastname: Hatae
authors.forename: Nozomu
authors.initials: N
authors.lastname: Nishi
authors.forename: Nobukazu
authors.initials: N
authors.lastname: Araki
mesh_terms: D000818:Animals; D000918:Antibody Specificity; D007758:Ear, Inner / Q000166:cytology / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D004705:Endocytosis / Q000502:physiology; D004710:Endolymph / Q000502:physiology*; D004712:Endolymphatic Sac / Q000378:metabolism* / Q000648:ultrastructure; D004847:Epithelial Cells / Q000378:metabolism / Q000648:ultrastructure; D015151:Immunoblotting; D007150:Immunohistochemistry; D007668:Kidney / Q000737:chemistry; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D008807:Mice, Inbred BALB C; D016253:Microscopy, Immunoelectron; D008861:Microsomes / Q000737:chemistry; D009928:Organ Specificity; D051381:Rats; D017207:Rats, Sprague-Dawley; D013680:Tectorial Membrane / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D026561:Low Density Lipoprotein Receptor-Related Protein-2