Oncomodulin is abundant in the organ of Corti

Henzl, Michael T.; Shibasaki, Osamu; Comegys, T. H.; Thalmann, Isolde; Thalmann, Ruediger

doi:10.1016/s0378-5955(97)00005-1

Cited by 35 publications

(41 citation statements)

References 47 publications

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“…We have determined that the Ca 2+ -binding protein parvalbumin 3 is abundant in the cytoplasm of hair cells in receptor organs of chickens, frogs, and zebra®sh. The mammalian ortholog of parvalbumin 3 may be oncomodulin (Henzl et al 1991), which has also been reported to occur in hair cells (Henzl et al 1997;Sakaguchi et al 1998). Parvalbumin 3 and related proteins should therefore be regarded as candidates to explain the Ca 2+ -buffering capacity of many varieties of hair cells.…”

Section: Discussionmentioning

confidence: 98%

“…1) and a calculated molecular mass of 12.4 kDa, parvalbumin 3 displays sequence homology to both muscle parvalbumin and avian thymic hormone, or parvalbumin 2, a secreted protein found in the chicken's thymus . Chicken parvalbumin 3 also resembles mammalian oncomodulin, a Ca 2+ -binding protein that has been observed in cochlear outer hair cells (Henzl et al 1997;Sakaguchi et al 1998).…”

Section: Cloning Of Cdnas Encoding Parvalbuminmentioning

confidence: 97%

“…Calretinin occurs in hair cells, including those of the mammalian cochlea (Dechesne et al 1991;Edmonds et al 2000). Hair cells also display immunoreactivity to conventional parvalbumin (Kerschbaum and Hermann 1993) and the related protein oncomodulin (Henzl et al 1997;Sakaguchi et al 1998). Found more commonly in supporting cells, S-100 is expressed by some hair cells as well (Saidel et al 1990).…”

Section: Introductionmentioning

confidence: 99%

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Parvalbumin 3 is an Abundant Ca2+ Buffer in Hair Cells

Heller

Bell

Denis

et al. 2002

JARO - Journal of the Association for Research in Otolaryngolog

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Ca2+ signaling serves distinct purposes in different parts of a hair cell. The Ca 2+ concentration in stereocilia regulates adaptation and, through rapid transduction-channel reclosure, underlies ampli®ca-tion of mechanical signals. In presynaptic active zones, Ca 2+ mediates the exocytotic release of afferent neurotransmitter. At efferent synapses, Ca 2+ activates the K + channels that dominate the inhibitory postsynaptic potential. A copious supply of diffusible protein buffer isolates the three signals by restricting the spread of free Ca 2+ and limiting the duration of its action. Using cDNA subtraction and a gene expression assay based on in situ hybridization, we detected abundant expression of mRNAs encoding the Ca 2+ buffer parvalbumin 3 in bullfrog saccular and chicken cochlear hair cells. We cloned cDNAs encoding this protein from the corresponding inner-ear libraries and raised antisera against recombinant bullfrog parvalbumin 3. Immunohistochemical labeling indicated that parvalbumin 3 is a prominent Ca 2+ -binding protein in the compact, cylindrical hair cells of the bullfrog's sacculus, and occurs as well in the narrow, peanut-shaped hair cells of that organ. Using quantitative Western blot analysis, we ascertained that the concentration of parvalbumin 3 in saccular hair cells is approximately 3 mM. Parvalbumin 3 is therefore a signi®cant mobile Ca 2+ buffer, and perhaps the dominant buffer, in many types of hair cell. Moreover, parvalbumin 3 provides an early marker for developing hair cells in the frog, chicken, and zebra®sh.

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Section: Discussionmentioning

confidence: 98%

Section: Cloning Of Cdnas Encoding Parvalbuminmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

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Parvalbumin 3 is an Abundant Ca2+ Buffer in Hair Cells

Heller

Bell

Denis

et al. 2002

JARO - Journal of the Association for Research in Otolaryngolog

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“…An oncomodulin dilution curve was included in each gel. Gels were scanned, and the concentration of the oncomodulin band (identified previously by antibodies and sequencing [19], was determined by integration and comparison with the oncomodulin standard curve using software from IO Informatics (http://www.ioinformatics.com/).…”

Section: Iefmentioning

confidence: 99%

Microscale analysis of proteins in inner ear tissues and fluids with emphasis on endolymphatic sac, otoconia, and organ of Corti

Thalmann

Hughes²,

Tong

et al. 2006

Electrophoresis

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Here we describe preparatory techniques adapted for the study of proteins of inner ear tissues and fluids that have allowed us to apply state-of-the-art analytical techniques in spite of the minute size and anatomical complexities of this organ. Illustrative examples address unresolved issues of functional and clinical significance. First, we demonstrate how quick-freezing and freeze drying prevents artifacts that arise from sampling endolymphatic sac (ES) content in the liquid state. This set the stage for the generation of the first protein profile of the ES. Identification of crucial proteins will help elucidate mechanisms of endolymph volume regulation and pathogenesis of Meniere's disease. Second, we show how a unique situation allowed identification of otoconial proteins by mass spectrometric analysis without prior separation and we discuss possible roles for these minor otoconins in otoconial development and prevention of degenerative diseases that affect balance. Finally, we demonstrate techniques for the precise dissection of organ of Corti and its substructures, while preserving their near normal chemical state. We extended an earlier study in which we identified a novel calcium-binding protein by IEF, oncomodulin, localized in the outer hair cells and show here the applicability of prefractionation for the screening of calcium-binding proteins of organ of Corti. These studies demonstrate how advanced preparatory and analytical techniques can be applied to studies of the inner ear.

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“…The distribution of the b isoform, also called oncomodulin, is more limited. Until recently, the outer hair cell population in the organ of Corti was believed to be the sole site for expression in postnatal mammals (Henzl et al 1997;Sakaguchi et al 1998). However, Benowitz and colleagues have shown that oncomodulin is secreted by activated macrophages and functions as a potent nerve growth factor for retinal ganglion cells (Yin et al 2006).…”

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confidence: 99%

Solution structure of Ca²⁺‐free rat β‐parvalbumin (oncomodulin)

Henzl

Tanner

2007

Protein Science

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Relative to other parvalbumin isoforms, the mammalian b-parvalbumin (oncomodulin) displays attenuated divalent ion affinity. High-resolution structural data for the Ca 2+ -bound protein have provided little insight into the physical basis for this behavior, prompting an examination of the unliganded state. This article describes the solution structure and peptide backbone dynamics of Ca 2+ -free rat b-parvalbumin (b-PV). Ca 2+ removal evidently provokes significant structural alterations. Interaction between the D helix and the AB domain in the Ca 2+ -bound protein is greatly diminished in the apo-form, permitting the D helix to straighten. There is also a significant reorganization of the hydrophobic core and a concomitant remodeling of the interface between the AB and CD-EF domains. These modifications perturb the orientation of the C and D helices, and the energetic penalty associated with their reversal could contribute to the low-affinity signature of the CD site. By contrast, Ca 2+ removal causes a comparatively minor perturbation of the E and F helices, consistent with the more typical divalent ion affinity observed for the EF site. Ca 2+ -free rat b-PV retains structural rigidity on the picosecond-nanosecond timescale. At 20°C, the majority of amide vectors show no evidence for motion on timescales above 20 ps, and the average order parameter for the entire molecule is 0.92.Keywords: calcium-binding protein; EF-hand protein; parvalbumin; oncomodulin; NMR; structure; dynamics Supplemental material: see www.proteinscience.orgThe role of Ca 2+ in eukaryotic signal transduction (Berridge et al. 2003;Berridge 2004Berridge , 2005) is facilitated by myriad Ca 2+ -binding proteins. Many of these exhibit a metal ion-binding site consisting of a central binding loop and flanking helical segments. This motif is commonly known as the ''EF-hand'' because the arrangement of the loop and helices can be mimicked with the fingers of the right hand (Kretsinger 1980;Kawasaki and Kretsinger 1995;Celio et al. 1996).Within the binding loop, the ligands to the bound ion are positioned at the vertices of an octahedron and, accordingly, are referenced by the axes of a Cartesian Reprint requests to: Michael T. Henzl, Department of Biochemistry, 117 Schweitzer Hall, University of Missouri-Columbia, Columbia, MO 65211, USA; e-mail: henzlm@missouri.edu; fax: (573) 884-4812.Abbreviations: ADR, ambiguous distance restraint; CD site, parvalbumin metal ion-binding site flanked by the C and D helices; CSI, chemical shift index; D a , axial component of the molecular alignment tensor; D k , principal axis component of the molecular diffusion tensor; D t , minor axis component of the molecular diffusion tensor in an axially symmetric system; DSS, sodium 2,2-dimethyl-2-silapentane-5-sulfonate; EDTA, ethylenediaminetetraacetic acid; EF site, parvalbumin metal ion-binding site flanked by the E and F helices; HEPES, 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid; HSQC, heteronuclear single-quantum coherence; Mes, 2-(N-morpholino)et...

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Oncomodulin is abundant in the organ of Corti

Cited by 35 publications

References 47 publications

Parvalbumin 3 is an Abundant Ca2+ Buffer in Hair Cells

Parvalbumin 3 is an Abundant Ca2+ Buffer in Hair Cells

Microscale analysis of proteins in inner ear tissues and fluids with emphasis on endolymphatic sac, otoconia, and organ of Corti

Solution structure of Ca²⁺‐free rat β‐parvalbumin (oncomodulin)

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Oncomodulin is abundant in the organ of Corti

Cited by 35 publications

References 47 publications

Parvalbumin 3 is an Abundant Ca2+ Buffer in Hair Cells

Parvalbumin 3 is an Abundant Ca2+ Buffer in Hair Cells

Microscale analysis of proteins in inner ear tissues and fluids with emphasis on endolymphatic sac, otoconia, and organ of Corti

Solution structure of Ca2+‐free rat β‐parvalbumin (oncomodulin)

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Solution structure of Ca²⁺‐free rat β‐parvalbumin (oncomodulin)