PDZD7-MYO7A complex identified in enriched stereocilia membranes

Morgan, Clive P.; Krey, Jocelyn F.; Grati, M’hamed; Zhao, Bo; Fallen, Shannon; Kannan-Sundhari, Abhiraami; Liu, Xue Zhong; Choi, Dongseok; Müller, Ulrich; Barr-Gillespie, Peter G.

doi:10.7554/elife.18312

Cited by 40 publications

(46 citation statements)

References 88 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additionally, without Myo7a, hair bundles must be deflected beyond their physiological operating range to open the MET channel [69]. More recently, it was shown that Myo7a interacts and colocalizes with PDZD7 at the ankle-link region of stereocilia [72 •• ]. This structure couples stereocilia at their base to maintain hair bundle morphology during development [73,74].…”

Section: Myth4-ferm Myosin Cargoes and Physiological Functionsmentioning

confidence: 99%

“…Although an early study suggested that the actin bundle of stereocilia treadmills [149], subsequent studies agree that stereocilia actin bundles are stable and actin turnover occurs only at the tips of core bundle actin filaments [150 • ,151 • ]. With the development of a new system for growing and maintaining hair cells in organoid cultures [152 •• ], as well as advances in stereocilia proteomic analyses that allow for identification of new low abundance proteins and protein complexes [72 •• ], research in the stereocilia field is poised to make key advances in the near future.…”

mentioning

confidence: 99%

See 1 more Smart Citation

MyTH4-FERM myosins in the assembly and maintenance of actin-based protrusions

Weck

Grega-Larson

Tyska

2017

Current Opinion in Cell Biology

View full text Add to dashboard Cite

Unconventional myosins are actin-based molecular motors that serve a multitude of roles within the cell, contributing to cell shape and function. One group of myosin motors, MyTH4-FERM myosins, plays an integral part in building and maintaining finger-like protrusions, which allows cells to interact with their external environment. Suggested to act primarily as transporters, these motor proteins enrich adhesion molecules, actin-regulatory proteins and other factors at the tips of filopodia, microvilli, and stereocilia. Below we review data from biophysical, biochemical, and cell biological studies, which implicate these myosins as central players in the assembly, maintenance and function of actin-based protrusions.

show abstract

Section: Myth4-ferm Myosin Cargoes and Physiological Functionsmentioning

confidence: 99%

mentioning

confidence: 99%

MyTH4-FERM myosins in the assembly and maintenance of actin-based protrusions

Weck

Grega-Larson

Tyska

2017

Current Opinion in Cell Biology

View full text Add to dashboard Cite

show abstract

“…[4][5][6] Evidences suggest that the USH2 proteins localize at the ankle region of hair cell stereocilia, where they bind to each other and form the so-called ankle-link complex. 11,18,19 PDZD7 disruption in mice causes stereocilia disorganization and MET deficits, leading to congenital hearing loss. PDZD7 contains three PDZ domains, a harmonin-N like (HNL) domain as well as a proline-rich (PR) region.…”

Section: Introductionmentioning

confidence: 99%

“…[14][15][16][17] PDZD7 also interacts with USH1 proteins harmonin, SANS (USH1G), and MYO7A (USH1B) in vitro. 11,18,19 PDZD7 disruption in mice causes stereocilia disorganization and MET deficits, leading to congenital hearing loss. 16 Noticeably, localization of all the three known USH2 proteins at the ankle region of the stereocilia is affected by PDZD7 disruption, suggesting that PDZD7 plays a pivotal role in organizing the ankle-link complex in the developing cochlear hair cells.…”

Section: Introductionmentioning

confidence: 99%

Lack of PDZD7 long isoform disrupts ankle‐link complex and causes hearing loss in mice

Zou

Ren

et al. 2019

FASEB j.

View full text Add to dashboard Cite

Usher syndrome (USH) is the most frequent form of combined hereditary deafnessblindness, characterized by hearing loss and retinitis pigmentosa, with or without vestibular dysfunction. PDZD7 is a PDZ domain-containing scaffold protein that was suggested to be a USH modifier and a contributor to digenic USH. In the inner ear hair cells, PDZD7 localizes at the ankle region of the stereocilia and constitutes the so-called ankle-link complex together with three other USH proteins Usherin, WHRN, and ADGRV1. PDZD7 gene is subjected to alternative splicing, which gives rise to two types of PDZD7 isoforms, namely the long and short isoforms. At present, little is known which specific isoform is involved in ankle-link formation and stereocilia development. In this work, we showed that PDZD7 long isoform, but not short isoforms, localizes at the ankle region of the stereocilia. Moreover, we established Pdzd7 mutant mice by introducing deletions into exon 14 of the Pdzd7 gene, which causes potential premature translational stop in the long isoform but leaves short isoforms unaffected. We found that lack of PDZD7 long isoform affects the localization of other ankle-link complex components in the stereocilia. Consequently, Pdzd7 mutant mice showed stereocilia development deficits and hearing loss as well as reduced mechanotransduction (MET) currents, suggesting that PDZD7 long isoform is indispensable for hair cells. Furthermore, by performing yeast two-hybrid screening, we identified a PDZD7 long isoform-specific binding partner PIP5K1C, which has been shown to play important roles in hearing and might participate in the function and/or transportation of PDZD7. F I G U R E 1 PDZD7 long isoform, but not short isoform, localizes in the stereocilia of auditory hair cells. A, Schematic drawing of Pdzd7 genomic structure and the domain architecture of PDZD7 protein. Mouse Pdzd7 gene contains 16 exons, and deletions were introduced into exon 14 that is unique for PDZD7 long isoform. The coding sequences were indicated by black boxes, whereas the uncoding sequences were indicated by grey boxes. The various domains and the antigens recognized by different antibodies were indicated. B and C, Cochlear whole mounts from Pdzd7 +/△PDZ3 and Pdzd7 △PDZ3/△PDZ3 mice at P4 were stained with PDZD7_C antibody (B) or PDZD7_N antibody (C). Phalloidin staining was also performed to indicate the stereocilia. Images were taken from the middle turn of the cochlea. D-E', Cochlear explants from wild-type mice at P3 were injectoporated with expression vectors to express HA-tagged PDZD7 long isoform (D and D') or short isoform (E and E') in hair cells. GFP fluorescence indicated successfully injectoporated hair cells. Immunostaining with anti-HA antibody was performed to locate HA-PDZD7. Phalloidin staining was performed to indicate the stereocilia. Scale bars: 2 μm in (B) and (C), 20 μm in (D) and (E), and 5 μm in (D') and (E')

show abstract

“…In addition, unconventional myosins also serve as actin-to-membrane connectors throughout the stereocilium (Hasson et al, 1997). For example, MYO6 localizes towards the proximal end of stereocilia (Hasson et al, 1997), MYO7A along the entire shaft (Morgan et al, 2016), and MYO3A, MYO3B, and MYO15A at stereocilia tips (Belyantseva et al, 2003, Schneider et al, 2006, Merritt et al, 2012). The location of MYO1C is controversial; it is either concentrated at the upper tip link insertion side (Garcia et al, 1998, Steyger et al, 1998), where adaptation is thought to occur, or is found throughout the stereocilia membrane (Belyantseva et al, 2005).…”

Section: Introductionmentioning

confidence: 99%