Identifying components of the hair-cell interactome involved in cochlear amplification

Jing Zheng, Charles T. Anderson, Katharine K. Miller, Mary Ann Cheatham, Peter Dallos

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background: Although outer hair cells (OHCs) play a key role in cochlear amplification, it is not fully understood how they amplify sound signals by more than 100 fold. Two competing or possibly complementary mechanisms, stereocilia-based and somatic electromotility-based amplification, have been considered. Lacking knowledge about the exceptionally rich protein networks in the OHC plasma membrane, as well as related protein-protein interactions, limits our understanding of cochlear function. Therefore, we focused on finding protein partners for two important membrane proteins: Cadherin 23 (cdh23) and prestin. Cdh23 is one of the tip-link proteins involved in transducer function, a key component of mechanoelectrical transduction and stereocilia-based amplification. Prestin is a basolateral membrane protein responsible for OHC somatic electromotility. Results: Using the membrane-based yeast two-hybrid system to screen a newly built cDNA library made predominantly from OHCs, we identified two completely different groups of potential protein partners using prestin and cdh23 as bait. These include both membrane bound and cytoplasmic proteins with 12 being de novo gene products with unknown function(s). In addition, some of these genes are closely associated with deafness loci, implying a potentially important role in hearing. The most abundant prey for prestin (38%) is composed of a group of proteins involved in electron transport, which may play a role in OHC survival. The most abundant group of cdh23 prey (55%) contains calcium-binding domains. Since calcium performs an important role in hair cell mechanoelectrical transduction and amplification, understanding the interactions between cdh23 and calcium-binding proteins should increase our knowledge of hair cell function at the molecular level. Conclusion: The results of this study shed light on some protein networks in cochlear hair cells. Not only was a group of de novo genes closely associated with known deafness loci identified, but the data also indicate that the hair cell tip link interacts directly with calcium binding proteins. The OHC motor protein, prestin, also appears to be associated with electron transport proteins. These unanticipated results open potentially fruitful lines of investigation into the molecular basis of cochlear amplification.

Original languageEnglish (US)
Article number127
JournalBMC Genomics
Volume10
DOIs
StatePublished - Mar 25 2009

Fingerprint

Outer Auditory Hair Cells
Cochlea
Cellular Structures
Cadherins
Proteins
Stereocilia
Calcium-Binding Proteins
Cell Membrane
Deafness
Electron Transport
Membrane Proteins
Auditory Hair Cells
Genes
Calcium
Two-Hybrid System Techniques
Transducers
Gene Library
Hearing
Cell Survival
Carrier Proteins

ASJC Scopus subject areas

  • Biotechnology
  • Genetics

Cite this

Zheng, Jing ; Anderson, Charles T. ; Miller, Katharine K. ; Cheatham, Mary Ann ; Dallos, Peter. / Identifying components of the hair-cell interactome involved in cochlear amplification. In: BMC Genomics. 2009 ; Vol. 10.
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abstract = "Background: Although outer hair cells (OHCs) play a key role in cochlear amplification, it is not fully understood how they amplify sound signals by more than 100 fold. Two competing or possibly complementary mechanisms, stereocilia-based and somatic electromotility-based amplification, have been considered. Lacking knowledge about the exceptionally rich protein networks in the OHC plasma membrane, as well as related protein-protein interactions, limits our understanding of cochlear function. Therefore, we focused on finding protein partners for two important membrane proteins: Cadherin 23 (cdh23) and prestin. Cdh23 is one of the tip-link proteins involved in transducer function, a key component of mechanoelectrical transduction and stereocilia-based amplification. Prestin is a basolateral membrane protein responsible for OHC somatic electromotility. Results: Using the membrane-based yeast two-hybrid system to screen a newly built cDNA library made predominantly from OHCs, we identified two completely different groups of potential protein partners using prestin and cdh23 as bait. These include both membrane bound and cytoplasmic proteins with 12 being de novo gene products with unknown function(s). In addition, some of these genes are closely associated with deafness loci, implying a potentially important role in hearing. The most abundant prey for prestin (38{\%}) is composed of a group of proteins involved in electron transport, which may play a role in OHC survival. The most abundant group of cdh23 prey (55{\%}) contains calcium-binding domains. Since calcium performs an important role in hair cell mechanoelectrical transduction and amplification, understanding the interactions between cdh23 and calcium-binding proteins should increase our knowledge of hair cell function at the molecular level. Conclusion: The results of this study shed light on some protein networks in cochlear hair cells. Not only was a group of de novo genes closely associated with known deafness loci identified, but the data also indicate that the hair cell tip link interacts directly with calcium binding proteins. The OHC motor protein, prestin, also appears to be associated with electron transport proteins. These unanticipated results open potentially fruitful lines of investigation into the molecular basis of cochlear amplification.",
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Identifying components of the hair-cell interactome involved in cochlear amplification. / Zheng, Jing; Anderson, Charles T.; Miller, Katharine K.; Cheatham, Mary Ann; Dallos, Peter.

In: BMC Genomics, Vol. 10, 127, 25.03.2009.

Research output: Contribution to journalArticle

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