Functional regulation of the SLC26-family protein prestin by calcium/calmodulin

Jacob Pearson Keller, Kazuaki Homma, Chongwen Duan, Jing Zheng, Mary Ann Cheatham, Peter Dallos*

*Corresponding author for this work

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

The solute carrier gene family 26 (SLC26) encodes membrane proteins with diverse physiological roles but with the common feature of halide involvement. Here, we present bioinformatic and biochemical evidence that SLC26 proteins have intrinsically disordered regions (IDRs) in their C-terminal domains and that these regions contain calmodulin (CaM) binding sites. The veracity of these predictions and the functional consequences of CaM binding were examined in prestin, SLC26A5, as a model for the SLC26 family and as one of the most investigated and best understood members. We found that CaM binds directly to the IDR in the C-terminal domain of prestin in a calcium-obligate manner. Using both isolated murine outer hair cells (OHCs) and a heterologous expression system, we also found that this calcium-obligate CaM binding shifts the operating point of the protein to more hyperpolarized potentials with consequent alteration of the function of the prestin. Because calcium is the main intracellular second messenger used by the efferent medial olivocochlear (MOC) pathway of the auditory system andCaMis abundant in OHCs, the CaM-prestin interactionmaybe involved in the MOC-mediated modulation of cochlear amplification. However, this regulatory mechanism is not likely to be restricted to cochlear OHCs, in light of both clear bioinformatic evidence and the fact that calcium and CaM are ubiquitous intracellular second messengers used by virtually all cell types. Hence, the calcium/CaM-dependent regulatory mechanism described herein is likely applicable to most, if not all, SLC26 paralogs.

Original languageEnglish (US)
Pages (from-to)1325-1332
Number of pages8
JournalJournal of Neuroscience
Volume34
Issue number4
DOIs
StatePublished - Jan 27 2014

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Keywords

  • Calmodulin
  • Disordered region
  • Mice
  • Prestin
  • SLC26 family

ASJC Scopus subject areas

  • Neuroscience(all)

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