Evidence map›Paper›PMID 38948700›Full record

ArticlebioRxiv : the preprint server for biology2024

Elasticity and Thermal Stability are Key Determinants of Hearing Rescue by Mini-Protocadherin-15 Proteins.

Pedro De-la-Torre, Haosheng Wen, Joseph Brower, Karina Martínez-Pérez, Yoshie Narui, Frank Yeh, Evan Hale, Maryna V Ivanchenko, David P Corey, Marcos Sotomayor and 1 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Pedro De-la-TorreDepartment of Otolaryngology - Head and Neck Surgery, Harvard Medical School and Massachusetts Eye and Ear, 243 Charles St, Boston, MA, USA.ORCID 0000-0002-2434-3345
Haosheng WenDepartment of Chemistry and Biochemistry, The Ohio State University, 484 W. 12th Avenue, Columbus, OH, USA.
Joseph BrowerDepartment of Otolaryngology - Head and Neck Surgery, Harvard Medical School and Massachusetts Eye and Ear, 243 Charles St, Boston, MA, USA.
Karina Martínez-PérezDepartment of Otolaryngology - Head and Neck Surgery, Harvard Medical School and Massachusetts Eye and Ear, 243 Charles St, Boston, MA, USA.
Yoshie NaruiCenter for Electron Microscopy and Analysis, The Ohio State University, 1275-1305 Kinnear Road, Columbus, OH, USA.
Frank YehDepartment of Otolaryngology - Head and Neck Surgery, Harvard Medical School and Massachusetts Eye and Ear, 243 Charles St, Boston, MA, USA.
Evan HaleDepartment of Otolaryngology - Head and Neck Surgery, Harvard Medical School and Massachusetts Eye and Ear, 243 Charles St, Boston, MA, USA.
Maryna V IvanchenkoDepartment of Neurobiology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA.
David P CoreyDepartment of Neurobiology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA.
Marcos SotomayorDepartment of Chemistry and Biochemistry, The Ohio State University, 484 W. 12th Avenue, Columbus, OH, USA.
Artur A IndzhykulianDepartment of Otolaryngology - Head and Neck Surgery, Harvard Medical School and Massachusetts Eye and Ear, 243 Charles St, Boston, MA, USA.ORCID 0000-0002-2076-6818

Funding

User Training and OutreachP30GM124165 · NIGMS · CORNELL UNIVERSITY · PI STEVEN E EALICK · 2018 to 2026
$34.2M
Molecular Basis of Hair Cell Stereocilia Bundle MorphologyR01DC017166 · NIDCD · MASSACHUSETTS EYE AND EAR INFIRMARY · PI INDZHYKULIAN, ARTUR · 2018 to 2022
$3.5M
Development of Gene Therapy for Hereditary Deafness using Rational Protein EngineeringR01DC020190 · NIDCD · MASSACHUSETTS EYE AND EAR INFIRMARY · PI DAVID P COREY, Artur Indzhykulian · 2022 to 2026
$3.3M
Pixel Array Detector for Macromolecular CrystallographyS10OD021527 · OD · CORNELL UNIVERSITY · PI EALICK, STEVEN E · 2016 to 2016
$2.0M
NIDCD NIH HHS R01 DC017166NIDCD NIH HHS R01 DC020190NIGMS NIH HHS P30 GM124165NIH HHS S10 OD021527
6 · The paper itself

Abstract

Protocadherin-15 is a core protein component of inner-ear hair-cell tip links pulling on transduction channels essential for hearing and balance. Protocadherin-15 defects can result in non-syndromic deafness or Usher syndrome type 1F (USH1F) with hearing loss, balance deficits, and progressive blindness. Three rationally engineered shortened versions of protocadherin-15 (mini-PCDH15s) amenable for gene therapy have been used to rescue function in USH1F mouse models. Two can successfully or partially rescue hearing, while another one fails. Here we show that despite varying levels of hearing rescue, all three mini-PCDH15 versions can rescue hair-cell mechanotransduction. Negative-stain electron microscopy shows that all three versions form dimers like the wild-type protein, while crystal structures of some engineered fragments show that these can properly fold and bind calcium ions essential for function. In contrast, simulations predict distinct elasticities and nano differential scanning fluorimetry shows differences in melting temperature measurements. Our data suggest that elasticity and thermal stability are key determinants of sustained hearing rescue by mini-PCDH15s.

Identifiers

PMID38948700
PMCPMC11212938

What OpenQuestion holds

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LicenceCC BY-NC
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.