title: Annexin A5 is the Most Abundant Membrane-Associated Protein in Stereocilia but is Dispensable for Hair-Bundle Development and Function.
abstract: The phospholipid- and Ca(2+)-binding protein annexin A5 (ANXA5) is the most abundant membrane-associated protein of ~P23 mouse vestibular hair bundles, the inner ear's sensory organelle. Using quantitative mass spectrometry, we estimated that ANXA5 accounts for ~15,000 copies per stereocilium, or ~2% of the total protein there. Although seven other annexin genes are expressed in mouse utricles, mass spectrometry showed that none were present at levels near ANXA5 in bundles and none were upregulated in stereocilia of Anxa5(-/-) mice. Annexins have been proposed to mediate Ca(2+)-dependent repair of membrane lesions, which could be part of the repair mechanism in hair cells after noise damage. Nevertheless, mature Anxa5(-/-) mice not only have normal hearing and balance function, but following noise exposure, they are identical to wild-type mice in their temporary or permanent changes in hearing sensitivity. We suggest that despite the unusually high levels of ANXA5 in bundles, it does not play a role in the bundle's key function, mechanotransduction, at least until after two months of age in the cochlea and six months of age in the vestibular system. These results reinforce the lack of correlation between abundance of a protein in a specific compartment or cellular structure and its functional significance.
authors.affiliation: Oregon Hearing Research Center, Oregon Health &Science University, Portland, OR 97239, USA.|Vollum Institute, Oregon Health &Science University, Portland, OR 97239, USA.
authors.forename: Jocelyn F
authors.initials: JF
authors.lastname: Krey
authors.affiliation: Department of Microbiology &Molecular Genetics, Department of Pediatrics &Human Development, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: Meghan
authors.initials: M
authors.lastname: Drummond
authors.affiliation: Oregon Hearing Research Center, Oregon Health &Science University, Portland, OR 97239, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Foster
authors.affiliation: Oregon Hearing Research Center, Oregon Health &Science University, Portland, OR 97239, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Porsov
authors.affiliation: Department of Special Education &Communication Disorders, University of Nebraska-Lincoln, Lincoln, NE 68583, USA.
authors.forename: Sarath
authors.initials: S
authors.lastname: Vijayakumar
authors.affiliation: School of Public Health, Oregon Health &Science University, Portland, OR 97239, USA.
authors.forename: Dongseok
authors.initials: D
authors.lastname: Choi
authors.affiliation: Department of Microbiology &Molecular Genetics, Department of Pediatrics &Human Development, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Friderici
authors.affiliation: Department of Special Education &Communication Disorders, University of Nebraska-Lincoln, Lincoln, NE 68583, USA.
authors.forename: Sherri M
authors.initials: SM
authors.lastname: Jones
authors.affiliation: Oregon Hearing Research Center, Oregon Health &Science University, Portland, OR 97239, USA.
authors.forename: Alfred L
authors.initials: AL
authors.lastname: Nuttall
authors.affiliation: Oregon Hearing Research Center, Oregon Health &Science University, Portland, OR 97239, USA.|Vollum Institute, Oregon Health &Science University, Portland, OR 97239, USA.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Barr-Gillespie
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000235:genetics* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D005072:Evoked Potentials, Auditory; D005260:Female; D055786:Gene Knockout Techniques; D006198:Hair Cells, Auditory / Q000502:physiology*; D008297:Male; D013058:Mass Spectrometry; D040542:Mechanotransduction, Cellular; D051379:Mice; D059547:Stereocilia / Q000378:metabolism*; D014722:Vestibule, Labyrinth / Q000254:growth & development* / Q000502:physiology
chemical_list: D017304:Annexin A5; C000627124:Anxa5 protein, mouse; D002118:Calcium