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BMC Genomics

, 10:127

First Online: 25 March 2009Received: 18 September 2008Accepted: 25 March 2009

Abstract

BackgroundAlthough 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.

ResultsUsing 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 functions.
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.

ConclusionThe 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.

AbbreviationsOHCsOuter hair cells

IHCsinner hair cells

cdh23Cadherin 23

OCorgan of Corti

METmechanoelectrical transduction

KOknockout

KIknock-in

PMplasma membrane

PCDH15protocadherin 15

UBPsubiquitin-specific proteases

CaMcalmodulin

S100A1S100 calcium binding protein A1

VAPAvesicle-associated membrane protein, associated protein A

ceacam16carcinoembryonic antigen-related cell adhesion molecule 16

LDSlithium dodecyl sulphate.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2164-10-127 contains supplementary material, which is available to authorized users.

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Autor: Jing Zheng - Charles T Anderson - Katharine K Miller - MaryAnn Cheatham - Peter Dallos

Fuente: https://link.springer.com/article/10.1186/1471-2164-10-127



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