title: 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.
abstract: 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.
authors.affiliation: Department of Otorhinolaryngology, Research Laboratory, Medical Faculty, Heinrich-Heine-University Düsseldorf, No. 23.12, Universitätsstr. 1, 40225, Düsseldorf, Germany, amzg@gmx.de.
authors.forename: A M
authors.initials: AM
authors.lastname: Meyer Zum Gottesberge
authors.forename: S
authors.initials: S
authors.lastname: Hansen
mesh_terms: D000818:Animals; D002465:Cell Movement; D003599:Cytoskeleton / Q000378:metabolism; D000070818:Discoidin Domain Receptors; D007758:Ear, Inner / Q000166:cytology* / Q000378:metabolism*; D018072:Hair Cells, Auditory, Outer / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D057507:Mice, 129 Strain; D024507:Nonmuscle Myosin Type IIA / Q000378:metabolism*; D009925:Organ of Corti / Q000166:cytology / Q000648:ultrastructure; D011485:Protein Binding; D020794:Receptor Protein-Tyrosine Kinases / Q000172:deficiency / Q000378:metabolism*; D038981:Receptors, Collagen / Q000378:metabolism*; D011975:Receptors, Mitogen / Q000172:deficiency / Q000378:metabolism*; D059547:Stereocilia / Q000378:metabolism
chemical_list: D038981:Receptors, Collagen; D011975:Receptors, Mitogen; D000070818:Discoidin Domain Receptors; D020794:Receptor Protein-Tyrosine Kinases; D024507:Nonmuscle Myosin Type IIA