scholarly journals ELMOD1 stimulates ARF6-GTP hydrolysis to stabilize apical structures in developing vestibular hair cells

2017 ◽  
Author(s):  
Jocelyn F. Krey ◽  
Rachel A. Dumont ◽  
Philip A. Wilmarth ◽  
Larry L. David ◽  
Kenneth R. Johnson ◽  
...  
Keyword(s):  
Hair Cells ◽  
Membrane Trafficking ◽  
Apical Membrane ◽  
Small Gtpase ◽  
Hair Bundle ◽  
Type I ◽  
Sensory Hair ◽  
Cuticular Plate ◽  
Sensory Hair Cells ◽  
Hair Bundles

AbstractSensory hair cells require control of physical properties of their apical plasma membranes for normal development and function. Members of the ARF small GTPase family regulate membrane trafficking and cytoskeletal assembly in many cells. We identified ELMOD1, a guanine nucleoside triphosphatase activating protein (GAP) for ARF6, as the most highly enriched ARF regulator in hair cells. To characterize ELMOD1 control of trafficking, we used a mouse strain lacking functional ELMOD1 (roundabout; rda). In rda/rda mice, cuticular plates of utricle hair cells initially formed normally, then degenerated after postnatal day 5 (P5); large numbers of vesicles invaded the compromised cuticular plate. Hair bundles initially developed normally, but the cell’s apical membrane lifted away from the cuticular plate, and stereocilia elongated and fused. Membrane trafficking in type I hair cells, measured by FM1-43 dye labeling, was altered in rda/rda mice. Consistent with the proposed GAP role for ELMOD1, the ARF6 GTP/GDP ratio was significantly elevated in rda/rda utricles as compared to controls, and the level of ARF6-GTP was correlated with the severity of the rda/rda phenotype. These results suggest that conversion of ARF6 to its GDP-bound form is necessary for final stabilization of the hair bundle.Significance StatementAssembly of the mechanically sensitive hair bundle of sensory hair cells requires growth and reorganization of apical actin and membrane structures. Hair bundles and apical membranes in mice with mutations in the Elmod1 gene degenerate after formation, suggesting that the ELMOD1 protein stabilizes these structures. We show that ELMOD1 is a GTPase-activating protein in hair cells for the small GTP-binding protein ARF6, known to participate in actin assembly and membrane trafficking. We propose that conversion of ARF6 into the GDP-bound form in the apical domain of hair cells is essential for stabilizing apical actin structures like the hair bundle and ensuring that the apical membrane forms appropriately around the stereocilia.

scholarly journals Multiple PDZ domain protein maintains patterning of the apical cytoskeleton in sensory hair cells

Development ◽  
2021 ◽  
Author(s):  
Amandine Jarysta ◽  
Basile Tarchini
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
Critical Role ◽  
Pdz Domain ◽  
Hair Bundle ◽  
Structural Defects ◽  
Sensory Hair ◽  
High Frequencies ◽  
Sensory Hair Cells ◽  
Sound Transduction

Sound transduction occurs in the hair bundle, the apical compartment of sensory hair cells in the inner ear. The hair bundle is formed of actin-based stereocilia aligned in rows of graded heights. It was previously shown that the GNAI-GPSM2 complex is part of a developmental blueprint that defines the polarized organization of the apical cytoskeleton in hair cells, including stereocilia distribution and elongation. Here we report a novel and critical role for Multiple PDZ domain (MPDZ) protein during apical hair cell morphogenesis. We show that MPDZ is enriched at the hair cell apical membrane along with MAGUK p55 subfamily member 5 (MPP5/PALS1) and the Crumbs protein CRB3. MPDZ is required there to maintain the proper segregation of apical blueprints proteins, including GNAI-GPSM2. Loss of the blueprint coincides with misaligned stereocilia placement in Mpdz mutant hair cells, and results in permanently misshapen hair bundles. Graded molecular and structural defects along the cochlea can explain the profile of hearing loss in Mpdz mutants, where deficits are most severe at high frequencies.

scholarly journals Multiple PDZ Domain Protein Maintains Patterning of the Apical Cytoskeleton in Sensory Hair Cells

2021 ◽  
Author(s):  
Amandine Jarysta ◽  
Basile Tarchini
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
Critical Role ◽  
Pdz Domain ◽  
Hair Bundle ◽  
Structural Defects ◽  
Sensory Hair ◽  
High Frequencies ◽  
Sensory Hair Cells ◽  
Sound Transduction

SUMMARYSound transduction occurs in the hair bundle, the apical compartment of sensory hair cells in the inner ear. The hair bundle is formed of stereocilia aligned in rows of graded heights. It was previously shown that the GNAI-GPSM2 complex is part of a developmental blueprint that defines the polarized organization of the apical cytoskeleton in hair cells, including stereocilia distribution and elongation. Here we report a novel and critical role for Multiple PDZ domain (MPDZ) protein during apical hair cell morphogenesis. We show that MPDZ is enriched at the hair cell apical membrane, and required there to maintain the proper segregation of apical blueprints proteins, including GNAI-GPSM2. Loss of the blueprint coincides with misaligned stereocilia in Mpdz mutants, and results in permanently misshapen hair bundles. Graded molecular and structural defects along the cochlea can explain the profile of hearing loss in Mpdz mutants, where deficits are most severe at high frequencies.

scholarly journals Stereocilia Rootlets: Actin-Based Structures That Are Essential for Structural Stability of the Hair Bundle

2020 ◽  
Vol 21 (1) ◽  
pp. 324 ◽  
Author(s):  
Itallia Pacentine ◽  
Paroma Chatterjee ◽  
Peter G. Barr-Gillespie
Keyword(s):  
Inner Ear ◽  
Hair Cells ◽  
Actin Filaments ◽  
Hair Bundle ◽  
Sensory Hair ◽  
Sensory Hair Cells ◽  
Associated Proteins ◽  
Unique Manner ◽  
Electrical Impulses ◽  
Mechanical Movement

Sensory hair cells of the inner ear rely on the hair bundle, a cluster of actin-filled stereocilia, to transduce auditory and vestibular stimuli into electrical impulses. Because they are long and thin projections, stereocilia are most prone to damage at the point where they insert into the hair cell’s soma. Moreover, this is the site of stereocilia pivoting, the mechanical movement that induces transduction, which additionally weakens this area mechanically. To bolster this fragile area, hair cells construct a dense core called the rootlet at the base of each stereocilium, which extends down into the actin meshwork of the cuticular plate and firmly anchors the stereocilium. Rootlets are constructed with tightly packed actin filaments that extend from stereocilia actin filaments which are wrapped with TRIOBP; in addition, many other proteins contribute to the rootlet and its associated structures. Rootlets allow stereocilia to sustain innumerable deflections over their lifetimes and exemplify the unique manner in which sensory hair cells exploit actin and its associated proteins to carry out the function of mechanotransduction.

scholarly journals Steady-state stiffness of utricular hair cells depends on macular location and hair bundle structure

2011 ◽  
Vol 106 (6) ◽  
pp. 2950-2963 ◽  
Author(s):  
Corrie Spoon ◽  
W. J. Moravec ◽  
M. H. Rowe ◽  
J. W. Grant ◽  
E. H. Peterson
Keyword(s):  
Steady State ◽  
Hair Cells ◽  
Head Movement ◽  
Time Course ◽  
Hair Bundle ◽  
Type I ◽  
Response Dynamics ◽  
Functional Interpretation ◽  
Hair Bundles ◽  
Bundle Structure

Spatial and temporal properties of head movement are encoded by vestibular hair cells in the inner ear. One of the most striking features of these receptors is the orderly structural variation in their mechanoreceptive hair bundles, but the functional significance of this diversity is poorly understood. We tested the hypothesis that hair bundle structure is a significant contributor to hair bundle mechanics by comparing structure and steady-state stiffness of 73 hair bundles at varying locations on the utricular macula. Our first major finding is that stiffness of utricular hair bundles varies systematically with macular locus. Stiffness values are highest in the striola, near the line of hair bundle polarity reversal, and decline exponentially toward the medial extrastriola. Striolar bundles are significantly more stiff than those in medial (median: 8.9 μN/m) and lateral (2.0 μN/m) extrastriolae. Within the striola, bundle stiffness is greatest in zone 2 (106.4 μN/m), a band of type II hair cells, and significantly less in zone 3 (30.6 μN/m), which contains the only type I hair cells in the macula. Bathing bundles in media that break interciliary links produced changes in bundle stiffness with predictable time course and magnitude, suggesting that links were intact in our standard media and contributed normally to bundle stiffness during measurements. Our second major finding is that bundle structure is a significant predictor of steady-state stiffness: the heights of kinocilia and the tallest stereocilia are the most important determinants of bundle stiffness. Our results suggest 1) a functional interpretation of bundle height variability in vertebrate vestibular organs, 2) a role for the striola in detecting onset of head movement, and 3) the hypothesis that differences in bundle stiffness contribute to diversity in afferent response dynamics.

Vestibular Type I and Type II Hair Cells. 2: Morphometric Comparisons of Dissociated Pigeon Hair Cells

1997 ◽  
Vol 7 (5) ◽  
pp. 407-420
Author(s):  
Anthony J. Ricci ◽  
Stephen L. Cochran ◽  
Katherine J. Rennie ◽  
Manning J. Correia
Keyword(s):  
Hair Cells ◽  
Semicircular Canals ◽  
Columba Livia ◽  
Hair Bundle ◽  
Type I ◽  
Type Ii ◽  
Cell Groups ◽  
Hair Bundles

Morphometric properties of solitary hair cells dissociated from the semicircular canals (SCC), utricles (UTR), and lagenas (LAG) of adult white king pigeons, Columba livia, were compared. Measurements were made of the cell body, cuticular plate and hair bundle. Cells were divided into two groups: type 1 (group 1) was predominantly type I hair cells, and type 2 (group 3) was primarily type II hair cells. Comparisons are made initially between end organs for each group. A subpopulation of short otolith hair cells was identified. Quantitative comparisons between isolated type 1 and type 2 hair cells demonstrated that type 1 hair cells were more homogeneous both within and between vestibular end organs; while they had shorter, thinner neck regions, narrower apical surfaces, with longer and thinner bodies than did type 2 hair cells. Generally, for both type 1 and type 2 hair cells, two different hair bundle shapes were present, those (unimodal) with a single sharp taper from longest to shortest stereocilia, and those (bimodal) with an initial steep tape-followed by a less steep taper. An additional subtype of type 1 hair cells with short hair bundles was identified. SCC hair cells have fewer hair bundles with bimodal tapers across all cell groups when compared to UTR or LAG. All cell subtypes identified for dissociated hair cells were corroborated using histologic sections.

scholarly journals Directional selectivity of afferent neurons in zebrafish neuromasts is regulated by Emx2 in presynaptic hair cells

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Young Rae Ji ◽  
Sunita Warrier ◽  
Tao Jiang ◽  
Doris K Wu ◽  
Katie S Kindt
Keyword(s):  
Hair Cells ◽  
Hair Bundle ◽  
Afferent Neuron ◽  
Lateral Line System ◽  
Directional Selectivity ◽  
Afferent Neurons ◽  
Line System ◽  
Sensory Hair Cells ◽  
Innervation Patterns ◽  
Hair Bundles

The orientation of hair bundles on top of sensory hair cells (HCs) in neuromasts of the lateral line system allows fish to detect direction of water flow. Each neuromast shows hair bundles arranged in two opposing directions and each afferent neuron innervates only HCs of the same orientation. Previously, we showed that this opposition is established by expression of Emx2 in half of the HCs, where it mediates hair bundle reversal (<xref ref-type="bibr" rid="bib15">Jiang et al., 2017</xref>). Here, we show that Emx2 also regulates neuronal selection: afferent neurons innervate either Emx2-positive or negative HCs. In emx2 knockout and gain-of-function neuromasts, all HCs are unidirectional and the innervation patterns and physiological responses of the afferent neurons are dependent on the presence or absence of Emx2. Our results indicate that Emx2 mediates the directional selectivity of neuromasts by two distinct processes: regulating hair bundle orientation in HCs and selecting afferent neuronal targets.

scholarly journals Synaptically silent sensory hair cells in zebrafish are recruited after damage

2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Qiuxiang Zhang ◽  
Suna Li ◽  
Hiu-Tung C. Wong ◽  
Xinyi J. He ◽  
Alisha Beirl ◽  
...  
Keyword(s):  
Hair Cells ◽  
Sensory Hair ◽  
Sensory Hair Cells

Molecular anatomy and physiology of exocytosis in sensory hair cells

Cell Calcium ◽  
2012 ◽  
Vol 52 (3-4) ◽  
pp. 327-337 ◽  
Author(s):  
Mark A. Rutherford ◽  
Tina Pangršič
Keyword(s):  
Hair Cells ◽  
Sensory Hair ◽  
Anatomy And Physiology ◽  
Sensory Hair Cells ◽  
Molecular Anatomy

S-100 protein is a selective marker for sensory hair cells of the lateral line system in teleosts

2002 ◽  
Vol 329 (2) ◽  
pp. 133-136 ◽  
Author(s):  
F Abbate ◽  
S Catania ◽  
A Germanà ◽  
T González ◽  
B Diaz-Esnal ◽  
...  
Keyword(s):  
Lateral Line ◽  
Hair Cells ◽  
Lateral Line System ◽  
Selective Marker ◽  
Line System ◽  
Sensory Hair ◽  
Sensory Hair Cells ◽  
S 100

scholarly journals The microRNA-183/96/182 Cluster is Essential for Stereociliary Bundle Formation and Function of Cochlear Sensory Hair Cells

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Ruishuang Geng ◽  
David N Furness ◽  
Chithra K Muraleedharan ◽  
Jinsheng Zhang ◽  
Alain Dabdoub ◽  
...  
Keyword(s):  
Hair Cells ◽  
Sensory Hair ◽  
Sensory Hair Cells ◽  
And Function
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