PDZD7-MYO7A complex identified in enriched stereocilia membranes
| Autor: | Peter G. Barr-Gillespie, Clive P Morgan, Jocelyn F. Krey, Abhiraami Kannan-Sundhari, Bo Zhao, Dongseok Choi, M'hamed Grati, Ulrich Müller, Shannon Fallen, Xue Zhong Liu |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Mouse QH301-705.5 Stereocilia (inner ear) Science Sensory system Plasma protein binding Biology Myosins General Biochemistry Genetics and Molecular Biology Mass Spectrometry Stereocilia 03 medical and health sciences Mice Myosin medicine otorhinolaryngologic diseases Animals Inner ear auditory Biology (General) Vestibular system vestibular Membranes General Immunology and Microbiology General Neuroscience hair bundle General Medicine Anatomy Cell Biology Kinocilium Chicken Cell biology immunoaffinity 030104 developmental biology medicine.anatomical_structure Myosin VIIa Medicine Hair cell sense organs Carrier Proteins Neuroscience Research Article Protein Binding |
| Zdroj: | eLife eLife, Vol 5 (2016) |
| ISSN: | 2050-084X |
| Popis: | While more than 70 genes have been linked to deafness, most of which are expressed in mechanosensory hair cells of the inner ear, a challenge has been to link these genes into molecular pathways. One example is Myo7a (myosin VIIA), in which deafness mutations affect the development and function of the mechanically sensitive stereocilia of hair cells. We describe here a procedure for the isolation of low-abundance protein complexes from stereocilia membrane fractions. Using this procedure, combined with identification and quantitation of proteins with mass spectrometry, we demonstrate that MYO7A forms a complex with PDZD7, a paralog of USH1C and DFNB31. MYO7A and PDZD7 interact in tissue-culture cells, and co-localize to the ankle-link region of stereocilia in wild-type but not Myo7a mutant mice. Our data thus describe a new paradigm for the interrogation of low-abundance protein complexes in hair cell stereocilia and establish an unanticipated link between MYO7A and PDZD7. DOI: http://dx.doi.org/10.7554/eLife.18312.001 eLife digest Inside the inner ear, sensory cells called hair cells detect and respond to sounds and head movements. These cells have a mechanically sensitive structure called the hair bundle, which is made of many thin projections called stereocilia. The stereocilia are linked so that when they bend in response to a sound or head movement, the whole hair bundle moves as one. A protein called myosin VIIA (MYO7A) is thought to be involved in forming links at the base of stereocilia (so-called ‘ankle links’) and relaying signals from the stereocilia to the rest of the hair cell. However, it is not known how MYO7A interacts with the proteins that make up the ankle links. To address this question. Morgan, Krey et al. developed a new method for isolating groups of proteins from the inner ear of chick embryos that are only found in low quantities. Using this method, it was possible to isolate MYO7A along with other proteins it associates with. One of these proteins – called PDZD7 – is known to be part of ankle links. The next step following on from this work is to use this new method to study other important groups of proteins that are even more scarce in hair bundles. DOI: http://dx.doi.org/10.7554/eLife.18312.002 |
| Databáze: | OpenAIRE |
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