The collagen receptor DDR1 co-localizes with the non-muscle myosin IIA in mice inner ear and contributes to the cytoarchitecture and stability of motile cells. 2014

A M Meyer Zum Gottesberge, and S Hansen
Department of Otorhinolaryngology, Research Laboratory, Medical Faculty, Heinrich-Heine-University Düsseldorf, No. 23.12, Universitätsstr. 1, 40225, Düsseldorf, Germany, amzg@gmx.de.

Discoidin domain receptor 1 (DDR1) is a tyrosine kinase receptor activated by native collagen. DDRs regulate cell adhesion, migration and various other cell functions. Deletion of the DDR1 gene in mice is associated with a severe decrease in auditory function and substantial structural alterations in a heterogeneous group of cells, including cells containing actin/myosin contractile elements, e.g., outer hair cells (OHCs) (Meyer zum Gottesberge et al. Lab Invest, 88: 27-37, 2008). The non-muscle myosin heavy chain isoform IIA (NM-IIA), encoded by MYH9, is implicated in the regulation of cell spreading, cellular reshaping and movement and cell migration and adhesion. In this study, we identify DDR1 and NM-IIA co-localization in the type III fibrocytes (tension fibrocytes) of the spiral ligament, the OHCs and the stereocilia of both OHCs and inner hair cells. We show for the first time that DDR1 malfunction causes OHC deformation and the separation of the lateral wall, the location of the cellular motor responsible for the electromotile property, explicitly in those regions showing DDR1 and NM-IIA co-localization. On the basis of our results, we propose that DDR1 acts in concert with proteins of the actin/myosin complex to maintain mechanical forces in the inner ear and to stabilize OHC cellular shape for proper auditory signal transduction.

UI MeSH Term Description Entries
D007758 Ear, Inner The essential part of the hearing organ consists of two labyrinthine compartments: the bony labyrinthine and the membranous labyrinth. The bony labyrinth is a complex of three interconnecting cavities or spaces (COCHLEA; VESTIBULAR LABYRINTH; and SEMICIRCULAR CANALS) in the TEMPORAL BONE. Within the bony labyrinth lies the membranous labyrinth which is a complex of sacs and tubules (COCHLEAR DUCT; SACCULE AND UTRICLE; and SEMICIRCULAR DUCTS) forming a continuous space enclosed by EPITHELIUM and connective tissue. These spaces are filled with LABYRINTHINE FLUIDS of various compositions. Labyrinth,Bony Labyrinth,Ear, Internal,Inner Ear,Membranous Labyrinth,Bony Labyrinths,Ears, Inner,Ears, Internal,Inner Ears,Internal Ear,Internal Ears,Labyrinth, Bony,Labyrinth, Membranous,Labyrinths,Labyrinths, Bony,Labyrinths, Membranous,Membranous Labyrinths
D009925 Organ of Corti The spiral EPITHELIUM containing sensory AUDITORY HAIR CELLS and supporting cells in the cochlea. Organ of Corti, situated on the BASILAR MEMBRANE and overlaid by a gelatinous TECTORIAL MEMBRANE, converts sound-induced mechanical waves to neural impulses to the brain. Basilar Papilla,Corti's Organ,Spiral Organ,Corti Organ,Cortis Organ,Organ, Corti's,Organ, Spiral,Organs, Spiral,Papilla, Basilar,Spiral Organs
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D011975 Receptors, Mitogen Glycoprotein molecules on the surface of B- and T-lymphocytes, that react with molecules of antilymphocyte sera, lectins, and other agents which induce blast transformation of lymphocytes. Lectin Receptors,Mitogen Receptors,Receptors, Lectin,Mitogen Receptor,Receptor, Mitogen
D002465 Cell Movement The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell. Cell Migration,Locomotion, Cell,Migration, Cell,Motility, Cell,Movement, Cell,Cell Locomotion,Cell Motility,Cell Movements,Movements, Cell
D003599 Cytoskeleton The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. Cytoplasmic Filaments,Cytoskeletal Filaments,Microtrabecular Lattice,Cytoplasmic Filament,Cytoskeletal Filament,Cytoskeletons,Filament, Cytoplasmic,Filament, Cytoskeletal,Filaments, Cytoplasmic,Filaments, Cytoskeletal,Lattice, Microtrabecular,Lattices, Microtrabecular,Microtrabecular Lattices
D000070818 Discoidin Domain Receptors Receptor tyrosine kinases that bind COLLAGENS. They are characterized by the presence of extracellular DISCOIDIN DOMAINS that activate SIGNAL TRANSDUCTION PATHWAYS in response to collagen binding. They may also be cleaved by MATRIX METALLOPROTEINASES to mediate cell interactions with the EXTRACELLULAR MATRIX. DDR Proteins,Discoidin Domain Receptor,Proteins, DDR,Receptor, Discoidin Domain,Receptors, Discoidin Domain
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D057507 Mice, 129 Strain Strains of mice arising from a parental inbred stock that was subsequently used to produce substrains of knockout and other mutant mice with targeted mutations. 129 Mice,129 Mouse,129 Strain Mice,129 Strain Mouse,Bar Harbor 129 Mice,Bar Harbor 129 Mouse,Mice, 129,Mice, Strain 129,Mouse, 129,Mouse, 129 Strain,Strain 129 Mice,Strain Mice, 129

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