PDZD7-MYO7A complex identified in enriched stereocilia membranes.
Clive P MorganJocelyn F KreyM'hamed GratiBo ZhaoShannon FallenAbhiraami Kannan-SundhariXue Zhong LiuDongseok ChoiUlrich MüllerPeter G Barr-GillespiePublished in: eLife (2016)
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.
Keyphrases
- induced apoptosis
- mass spectrometry
- wild type
- cell cycle arrest
- genome wide
- minimally invasive
- endoplasmic reticulum stress
- signaling pathway
- liquid chromatography
- type diabetes
- cell death
- binding protein
- bone marrow
- high resolution
- ms ms
- electronic health record
- cell proliferation
- insulin resistance
- wastewater treatment
- deep learning
- big data
- small molecule
- mesenchymal stem cells
- genome wide analysis