| 2010 |
PDZD7 knockdown in zebrafish produced an Usher-like phenotype, exacerbated retinal cell death in combination with ush2a or gpr98 knockdown, and reduced Gpr98 localization in the region of the photoreceptor connecting cilium, establishing PDZD7 as a modifier of retinal disease and contributor to digenic Usher syndrome through genetic interaction with USH2A and GPR98. |
Zebrafish morpholino knockdown, epistasis/double-knockdown, immunolocalization |
The Journal of clinical investigation |
High |
20440071
|
| 2012 |
PDZD7 localizes to the ankle-link region of hair cell stereocilia, overlapping with usherin, whirlin, and GPR98; cytosolic domains of usherin and GPR98 can directly bind to both whirlin and PDZD7, establishing PDZD7 as a scaffolding component of the ankle-link complex. |
Mass spectrometry of chick stereocilia, immunofluorescence, overexpression of tagged proteins in rat/mouse hair cells, pull-down assays in LLC-PK1 cells |
The Journal of neuroscience |
High |
23055499
|
| 2013 |
Pdzd7 knockout mice exhibit congenital profound deafness with disorganized stereocilia bundles, reduced mechanotransduction currents, and loss of USH2 protein complex (USH2A, GPR98, WHRN) localization at ankle links in cochlear hair cells, demonstrating that PDZD7 is essential for organizing the USH2 complex at ankle links through direct interactions with all three USH2 proteins. |
Knockout mouse model, ABR/DPOAE/cochlear microphonics, electron microscopy, immunolocalization, electrophysiology |
Human molecular genetics |
High |
24334608
|
| 2014 |
PDZD7 overexpression decreased the adenylate cyclase inhibition mediated by the VLGR1 (ADGRV1) β-subunit Gαi coupling, identifying PDZD7 as a negative regulator of VLGR1 constitutive Gαi signaling activity. |
cAMP assay, co-expression in cell lines, functional mutant analysis |
The Journal of biological chemistry |
Medium |
24962568
|
| 2014 |
WHRN and PDZD7 are both required to form a quaternary USH2 protein complex with USH2A and GPR98; WHRN preferentially binds USH2A, PDZD7 preferentially binds GPR98, and WHRN-PDZD7 interaction bridges USH2A and GPR98 within the complex. |
Yeast two-hybrid, pull-down assays, colocalization in cell lines, systematic domain mapping |
The Journal of biological chemistry |
High |
25406310
|
| 2016 |
MYO7A forms a complex with PDZD7 in stereocilia membrane fractions; MYO7A and PDZD7 interact in tissue-culture cells, and PDZD7 co-localizes to the ankle-link region of stereocilia in wild-type but not Myo7a mutant mice, demonstrating that PDZD7 localization at ankle links depends on MYO7A. |
Stereocilia membrane fractionation, mass spectrometry, co-immunoprecipitation in tissue-culture cells, immunolocalization in Myo7a mutant mice |
eLife |
High |
27525485
|
| 2018 |
Yeast two-hybrid screening using the first two PDZ domains of PDZD7 as bait identified novel binding partners including ADGRV1, gelsolin, β-catenin, and CADM1, expanding the known PDZD7 interactome. |
Yeast two-hybrid screening, expression verification by RT-PCR/immunostaining, ABR measurement in Cadm1 KO mice |
Neural plasticity |
Medium |
29796015
|
| 2019 |
The PDZD7 long isoform, but not short isoforms, localizes to the ankle region of stereocilia; selective disruption of the long isoform in mice impairs ankle-link complex localization, causes stereocilia development deficits, reduces MET currents, and causes hearing loss; yeast two-hybrid identified PIP5K1C as a long-isoform-specific binding partner. |
Isoform-selective mouse knockout (exon 14 deletion), ABR, immunolocalization, electrophysiology, yeast two-hybrid |
FASEB journal |
High |
31914662
|
| 2021 |
The PDZD7 harmonin homology domain (HHD) adopts a five-helix fold and contains a unique α1N helix that occupies the canonical binding pocket; the HHD binds lipids and mediates localization of PDZD7 to the plasma membrane, and a hearing-loss mutation in the N-terminal extension of HHD disrupts lipid binding. |
X-ray crystallography (1.49 Å), lipid-binding assays, subcellular localization in HEK293T cells, disease mutation analysis |
Frontiers in cell and developmental biology |
High |
33937240
|
| 2022 |
Both N-terminal PDZ domains of PDZD7 bind the C-terminal PDZ-binding motif (PBM) of ADGRV1 via atypical C-terminal β extensions; the two PDZ domains form a supramodule in solution that is stabilized upon PBM binding; two deafness-causing mutations located in the binding grooves of these PDZ domains disrupt stability and binding. |
NMR, ITC, mutagenesis, structural biochemistry in solution |
Frontiers in molecular biosciences |
High |
35836927
|
| 2022 |
PDZD7 PDZ3 domain binds the C-terminal tail of FCHSD2 (a CDC42/N-WASP regulator of cell protrusion); crystal structure at 2.0 Å resolution shows the FCHSD2 PDZ-binding motif stretching through the αB/βB groove of PDZD7 PDZ3, linking the ankle-link complex to cytoskeletal dynamics. |
Yeast two-hybrid, co-immunoprecipitation in COS-7 cells, X-ray crystallography (2.0 Å) |
The Biochemical journal |
High |
35695292
|
| 2025 |
Using STED super-resolution nanoscopy, ADGRV1 and PDZD7 show highly asymmetric colocalization within stereocilia rows at the ankle-link region, with distinct distributions between inner and outer hair cells; the ADGRV1 extracellular domain disappears after P12 while the GPCR domain persists until P21, suggesting a signaling role beyond scaffolding. |
STED nanoscopy on juvenile mouse cochlear hair cells |
iScience |
Medium |
40836926
|
| 2008 |
Homozygous disruption of PDZD7 by chromosomal translocation causes non-syndromic congenital hearing loss; protein-protein interaction assays showed PDZD7 integrates into the Usher syndrome protein network; PDZD7 shares homology with harmonin (USH1C) and whirlin (DFNB31). |
FISH, junction fragment cloning/sequencing, RT-PCR for inner ear expression, protein-protein interaction assays |
Human molecular genetics |
Medium |
19028668
|