Hair Bundles Are Specialized for ATP Delivery via Creatine Kinase

Jung Bum Shin, Femke Streijger, Andy Beynon, Theo Peters, Laura Gadzala, Debra McMillen, Cory Bystrom, Catharina E.E.M. Van der Zee, Theo Wallimann, Peter G. Gillespie

Research output: Contribution to journalArticle

92 Scopus citations

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 Ca2+ regulation, and stress-response proteins, many of the most abundant bundle proteins that were identified by mass spectrometry were involved in ATP synthesis. After β-actin, the cytosolic brain isoform of creatine kinase was the next most abundant bundle protein; at ∼0.5 mM, creatine kinase is capable of maintaining high ATP levels despite 1 mM/s ATP consumption by the plasma-membrane Ca2+-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.

Original languageEnglish (US)
Pages (from-to)371-386
Number of pages16
JournalNeuron
Volume53
Issue number3
DOIs
StatePublished - Feb 1 2007

Keywords

  • MOLNEURO
  • SIGNALING

ASJC Scopus subject areas

  • Neuroscience(all)

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    Shin, J. B., Streijger, F., Beynon, A., Peters, T., Gadzala, L., McMillen, D., Bystrom, C., Van der Zee, C. E. E. M., Wallimann, T., & Gillespie, P. G. (2007). Hair Bundles Are Specialized for ATP Delivery via Creatine Kinase. Neuron, 53(3), 371-386. https://doi.org/10.1016/j.neuron.2006.12.021