title: Hair bundles are specialized for ATP delivery via creatine kinase.
abstract: When stimulated strongly, a hair cell's mechanically sensitive hair bundle may consume ATP too rapidly for replenishment by diffusion. To provide a broad view of the bundle's protein complement, including those proteins participating in energy metabolism, we used shotgun mass spectrometry methods to identify proteins of purified chicken vestibular bundles. In addition to cytoskeletal proteins, proteins involved in Ca(2+) regulation, and stress-response proteins, many of the most abundant bundle proteins that were identified by mass spectrometry were involved in ATP synthesis. After beta-actin, the cytosolic brain isoform of creatine kinase was the next most abundant bundle protein; at approximately 0.5 mM, creatine kinase is capable of maintaining high ATP levels despite 1 mM/s ATP consumption by the plasma-membrane Ca(2+)-ATPase. Consistent with this critical role in hair bundle function, the creatine kinase circuit is essential for high-sensitivity hearing as demonstrated by hearing loss in creatine kinase knockout mice.
authors.affiliation: Oregon Hearing Research Center and Vollum Institute, Oregon Health and Science University, Portland, OR 97239, USA.
authors.forename: Jung-Bum
authors.initials: JB
authors.lastname: Shin
authors.forename: Femke
authors.initials: F
authors.lastname: Streijger
authors.forename: Andy
authors.initials: A
authors.lastname: Beynon
authors.forename: Theo
authors.initials: T
authors.lastname: Peters
authors.forename: Laura
authors.initials: L
authors.lastname: Gadzala
authors.forename: Debra
authors.initials: D
authors.lastname: McMillen
authors.forename: Cory
authors.initials: C
authors.lastname: Bystrom
authors.forename: Catharina E E M
authors.initials: CE
authors.lastname: Van der Zee
authors.forename: Theo
authors.initials: T
authors.lastname: Wallimann
authors.forename: Peter G
authors.initials: PG
authors.lastname: Gillespie
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000201:enzymology; D002645:Chickens / Q000502:physiology*; D003402:Creatine Kinase / Q000235:genetics / Q000378:metabolism*; D003600:Cytosol / Q000201:enzymology; D007758:Ear, Inner / Q000201:enzymology / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D006198:Hair Cells, Auditory / Q000201:enzymology / Q000378:metabolism*; D006309:Hearing / Q000502:physiology; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism; D013058:Mass Spectrometry; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000145:classification / Q000378:metabolism; D004856:Postural Balance / Q000502:physiology; D011892:Rana catesbeiana; D012444:Saccule and Utricle / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: D007527:Isoenzymes; D009419:Nerve Tissue Proteins; D000255:Adenosine Triphosphate; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D003402:Creatine Kinase