Evidence map›Paper›PMID 20505086›Full record

ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2010

Targeting of the hair cell proteins cadherin 23, harmonin, myosin XVa, espin, and prestin in an epithelial cell model.

Lili Zheng, Jing Zheng, Donna S Whitlon, Jaime García-Añoveros, James R Bartles

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
2.3field-weighted citation impact, top 13% of its field
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

28 citing papers in PubMed, 40 citations in OpenAlex.

  1. Article
  2. Functional Studies of Deafness-Associated Pendrin and Prestin Variants.International journal of molecular sciences · 2024
    Article
  3. Review
  4. ARNSHL gene identification: past, present and future.Molecular genetics and genomics : MGG · 2022
    Review
  5. Article
  6. Usher Syndrome: Genetics of a Human Ciliopathy.International journal of molecular sciences · 2021
    Review
  7. Article
  8. Inframe deletion of humanJournal of medical genetics · 2018
    Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review
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

5 authors at 2 institutions in 2 countries.

Lili ZhengDepartment of Cell and Molecular Biology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
Jing Zheng
Donna S Whitlon
Jaime García-Añoveros
James R Bartles
Northwestern University · USInstitute of Molecular and Cell Biology · RU

Funding

MULTIDISCIPLINARY CLINICAL AND TRANSLATIONAL SCIENCE (MCTS) PROGRAM (UL1)UL1RR025741 · NCRR · NORTHWESTERN UNIVERSITY AT CHICAGO · PI GREENLAND, PHILIP · 2008 to 2011
$24.7M
THE ROLES OF ESPINS IN HAIR CELL STEREOCILIAR01DC004314 · NIDCD · NORTHWESTERN UNIVERSITY AT CHICAGO · PI BARTLES, JAMES R · 2000 to 2019
$8.0M
Molecular Basis of Somatic SensationR01NS044363 · NINDS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI GARCIA-ANOVEROS, JAIME · 2003 to 2013
$3.4M
DETERMINANTS OF NEURONAL CONNECTIVITY IN THE COCHLEAR01DC000653 · NIDCD · UNIVERSITY OF WISCONSIN MADISON · PI WHITLON, DONNA S. · 1995 to 2005
$1.6M
Investigating the nature of prestin-associated proteinsR01DC006412 · NIDCD · NORTHWESTERN UNIVERSITY · PI ZHENG, JING · 2005 to 2007
$867k
DETERMINANTS OF NEURONAL CONNECTIVITY IN THE COCHLEAR29DC000653 · NIDCD · UNIVERSITY OF WISCONSIN MADISON · PI WHITLON, DONNA S. · 1990 to 1994
–
NCRR NIH HHS UL1 RR025741NIDCD NIH HHS DC004314NIDCD NIH HHS DC006412NIDCD NIH HHS DC00653NIDCD NIH HHS R01 DC000653NIDCD NIH HHS R01 DC004314NIDCD NIH HHS R01 DC006412NINDS NIH HHS NS044363NINDS NIH HHS R01 NS044363
6 · The paper itself

Abstract

We have developed an advantageous epithelial cell transfection model for examining the targeting, interactions, and mutations of hair cell proteins. When expressed in LLC-PK1-CL4 epithelial cells (CL4 cells), the outer hair cell protein prestin showed faithful domain-specific targeting to the basolateral plasma membrane. We examined the consequences of mutations affecting prestin activity and assigned a targeting role to the cytoplasmic tail. The stereociliary link protein cadherin 23 (Cdh23) was targeted to the plasma membrane of CL4 cell microvilli, the topological equivalent of stereocilia. In cells coexpressing the Cdh23 cytoplasmic binding protein harmonin, a large fraction of harmonin became colocalized with Cdh23 in microvilli. Using this assay and in vitro protein binding assays, we formulated an alternative model for Cdh23-harmonin binding, in which the primary interaction is between the harmonin N-domain and a 35-residue internal peptide in the Cdh23 cytoplasmic tail. Contrary to a previous model, we found no role for the Cdh23 C-terminal PDZ (PSD-95/Dlg/ZO-1)-binding motif and observed that Cdh23 bound similar levels of harmonin with or without the exon 68 peptide. We also examined two proteins involved in stereocilium elongation. The stereociliary actin-bundling protein espin was targeted to CL4 cell microvilli and caused microvillar elongation, whereas espin with the c.2469delGTCA or c.1988delAGAG human deafness mutation showed defects in microvillar targeting and elongation. The unconventional myosin motor myosin XVa accumulated at the tips of espin-elongated microvilli, by analogy to its location in stereocilia, whereas myosin XVa with the c.4351G>A or c.4669A>G human deafness mutation did not, revealing functional deficits in motor activity.

Indexed as

Adaptor Proteins, Signal TransducingAnion Transport ProteinsCadherin Related ProteinsCadherinsCell Cycle ProteinsCell Line, TransformedCell MembraneCytoskeletal ProteinsEpithelial CellsGreen Fluorescent ProteinsHumansMicrofilament ProteinsMicrovilliModels, BiologicalMutagenesisMyosinsAdaptor Proteins, Signal TransducingAnion Transport ProteinsCadherin Related ProteinsCadherinsCDH23 protein, humanCell Cycle ProteinsCytoskeletal ProteinsESPN protein, humanGreen Fluorescent ProteinsMicrofilament ProteinsMYO15A protein, humanMyosinsSLC26A5 protein, humanSulfate TransportersUSH1C protein, human

Identifiers

PMID20505086
PMCPMC2989820
OpenAlexW2041255482

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.