Mechano-electrical Transduction: New Insights into Old Ideas

Ricci, Anthony J.; Kachar, Bechara; Gale, Jonathan E.; Netten, van Sietse

doi:10.1007/s00232-005-0834-8

Cited by 52 publications

(42 citation statements)

References 131 publications

(204 reference statements)

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“…Further, the instantaneous current is detected at high extracellular K ϩ (25), as would be present extracellularly in endolymph. Interestingly, structural investigations have suggested that the hair cell mechanosensory transduction channels "may be located only on the tops of the shorter stereocilia" (42,43), and it is the tops of shorter stereocilia that appear to represent the site of protocadherin 15 (CD3) localization, as opposed to cadherin 23, the other putative component of tip links with stereociliary insertion points localized midway along the taller stereocilia (8). Further, recent experiments point to the tips of the shorter stereocilia as sites for calcium entry, required in the adaptation phase of mechanosensory transduction, again consistent with colocalization of mechanosensory transduction channels and protocadherin 15 tip link insertion sites (44 -46).…”

Section: Discussionmentioning

confidence: 99%

Calcium-dependent Binding of HCN1 Channel Protein to Hair Cell Stereociliary Tip Link Protein Protocadherin 15 CD3

Ramakrishnan

Drescher

Barretto

et al. 2009

Journal of Biological Chemistry

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The cytoplasmic amino terminus of HCN1, the primary full-length HCN isoform expressed in trout saccular hair cells, was found by yeast two-hybrid protocols to bind the cytoplasmic carboxyl-terminal domain of a protocadherin 15a-like protein. HCN1 was immunolocalized to discrete sites on saccular hair cell stereocilia, consistent with gradated distribution expected for tip link sites of protocadherin 15a. HCN1 message was also detected in cDNA libraries of rat cochlear inner and outer hair cells, and HCN1 protein was immunolocalized to cochlear hair cell stereocilia. As predicted by the trout hair cell model, the amino terminus of rat organ of Corti HCN1 was found by yeast two-hybrid analysis to bind the carboxyl terminus of protocadherin 15 CD3, a tip link protein implicated in mechanosensory transduction. Specific binding between HCN1 and protocadherin 15 CD3 was confirmed with pull-down assays and surface plasmon resonance analysis, both predicting dependence on Ca HCN12 is the primary full-length HCN isoform underlying I h (hyperpolarization-activated, cyclic nucleotide-gated, nonselective cation channel current) in a model hair cell preparation from the trout sacccule (1). cAMP-gated I h , possibly in addition to the mechanosensory-transduction current, sets the membrane potential for a subpopulation of saccular hair cells (2, 3). The membrane potential in the saccular hair cell subpopulation is sufficiently depolarized to activate voltage-gated calcium channels, permitting influx of calcium and secretion of hair cell transmitter (2). Given that saccular hair cells expressing I K1 in addition to I h are more hyperpolarized, not supporting activation of the voltage-gated calcium channels, we predicted that spontaneous release of transmitter from the subpopulation of hair cells would constitute hair cell-generated spontaneous activity for the saccule (1). However, little has been previously reported on the morphological localization of the HCN1 isoform in hair cells or possible links to structural proteins that mechanistically would localize HCN1 in hair cells (for preliminary report, see Ref. 4). In general, little is known about proteinprotein interactions for the HCN isoforms that would modulate I h and/or the associated instantaneous current (5).Protocadherin 15 is a proposed tip link protein involved in connecting shorter stereocilia to adjacent taller stereocilia in the stereociliary array of inner ear hair cells, facilitating the opening of the mechanosensory transduction channel in response to auditory and vestibular stimuli. The active tip link protein in Danio rerio is protocadherin 15a (6), characterized by splice variants in its carboxyl terminus. In the mammal, protocadherin 15 CD3 is hypothesized to be a tip link protein at insertion sites in the tips of the shorter stereocilia of the stereociliary array (7,8). EXPERIMENTAL PROCEDURES Acquisition of a Model Hair Cell Preparation from the Trout Saccule and an Organ of Corti Subfraction from theRat Cochlea-Hair cell layers were isolated from the t...

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Section: Discussionmentioning

confidence: 99%

Calcium-dependent Binding of HCN1 Channel Protein to Hair Cell Stereociliary Tip Link Protein Protocadherin 15 CD3

Ramakrishnan

Drescher

Barretto

et al. 2009

Journal of Biological Chemistry

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“…While several mechanosensory units are membrane based proteins, nevertheless several such proteins belong to the soluble repertoire as well (Vogel, 2006;Vogel and Sheetz, 2006). Loss or aberrant mechanosensing and transduction of mechansensory signal may also be part of pathology in progressive hearing loss (Knoll et al, 2003;Ricci et al, 2006). Dysfunction or absence of any of the mechanosensing transmembrane molecules results in disruption of the network causing sensorineural degeneration in the inner ear and in the retina in Usher syndrome, another disease that leads to retinal degeneration and progressive hearing loss (Reiners et al, 2006), and other forms of progressive hearing losses such as DFNA4 and DFNB6 (Bearer et al, 2000;Mitchem et al, 2002).…”

Section: Cochlin and Extracellular Matrixmentioning

confidence: 99%

Cochlin in the eye: Functional implications

Picciani

Desai

Guduric-Fuchs

et al. 2007

Progress in Retinal and Eye Research

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Aqueous humor is actively produced in the ciliary epithelium of the anterior chamber and has important functions for the eye. Under normal physiological conditions, the inflow and outflow of the aqueous humor are tightly regulated, but in the pathologic state this balance is lost. Aqueous outflow involves structures of the anterior chamber and experiences most resistance at the level of the trabecular meshwork (TM) that acts as a filter. The modulation of the TM structure regulates the filter and its mechanism remains poorly understood. Proteomic analyses have identified cochlin, a protein of poorly understood function, in the glaucomatous TM but not in healthy control TM from human cadaver eyes. The presence of cochlin has subsequently been confirmed by Western and immunohistochemical analyses. Functionally, cochlin undergoes multimerization induced by shear stress and other changes in the microenvironment. Cochlin along with mucopolysaccharide deposits have been found in the TM of glaucoma patients and in the inner ear of subjects affected by the hearing disorder DNFA9, a late onset, progressive disease that also involves alterations in fluid shear regimes. In vitro, cochlin induces aggregation of primary TM cells suggesting a role in cell adhesion, possibly in mechanosensation, and in modulation of the TM filter.

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“…Many types of cells are reported to sense mechanical stimulation, which are transformed into intracellular signals [22,23]. With respect to regulators of cellular mechanical properties, Ca 2+ influx, integrin complex activation, and RhoA activation are known to act as first messengers [24].…”

Section: Resultsmentioning

confidence: 99%

The Number of Cyclic Stretch Regulates Cellular Elasticity in C2C12 Myoblasts

Takemoto¹,

Mizutani

Tamura³

et al. 2012

CellBio

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Mechanical stimulations have been shown to regulate cellular mechanical properties. However, the stimulation patterns for effective regulation are as yet unclear. We investigated the effects of application of differing numbers of mechanical stimulation sets, each set consisting of 8% extension and compression to cells via deformation of cell culture elastic chamber, on cellular elasticity. Elasticity increased with only a single step-like stretch and with a single step-like stretch after 1 set of mechanical stimulation, whereas elasticity did not change with a single step-like stretch after 10 sets of mechanical stimulation. These results indicate that the increase in cellular elasticity with the single step-like stretch depends on the number of applied mechanical stimulations. Immunofluorescence staining showed that phosphorylation and dephosphorylation of myosin regulatory light chain (MRLC), which regulates intracellular contractile force and cellular elasticity, accompanied cellular elasticity changes. These findings suggest that cellular elasticity changes under cyclic and step-like stretches are mediated by MRLC.

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Mechano-electrical Transduction: New Insights into Old Ideas

Cited by 52 publications

References 131 publications

Calcium-dependent Binding of HCN1 Channel Protein to Hair Cell Stereociliary Tip Link Protein Protocadherin 15 CD3

Calcium-dependent Binding of HCN1 Channel Protein to Hair Cell Stereociliary Tip Link Protein Protocadherin 15 CD3

Cochlin in the eye: Functional implications

The Number of Cyclic Stretch Regulates Cellular Elasticity in C2C12 Myoblasts

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