scholarly journals Author response: Synaptic mitochondria regulate hair-cell synapse size and function

2019 ◽  
Author(s):  
Hiu-tung C Wong ◽  
Qiuxiang Zhang ◽  
Alisha J Beirl ◽  
Ronald S Petralia ◽  
Ya-Xian Wang ◽  
...  
Keyword(s):  
Hair Cell ◽  
Author Response ◽  
Synaptic Mitochondria ◽  
And Function ◽  
Cell Synapse

scholarly journals Synaptic mitochondria regulate hair-cell synapse size and function

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Hiu-tung C Wong ◽  
Qiuxiang Zhang ◽  
Alisha J Beirl ◽  
Ronald S Petralia ◽  
Ya-Xian Wang ◽  
...  
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
Direct Application ◽  
Structural Protein ◽  
Ribbon Synapses ◽  
Presynaptic Function ◽  
Sensory Hair Cells ◽  
Synaptic Mitochondria ◽  
And Function ◽  
Cell Synapse

Sensory hair cells in the ear utilize specialized ribbon synapses. These synapses are defined by electron-dense presynaptic structures called ribbons, composed primarily of the structural protein Ribeye. Previous work has shown that voltage-gated influx of Ca2+ through CaV1.3 channels is critical for hair-cell synapse function and can impede ribbon formation. We show that in mature zebrafish hair cells, evoked presynaptic-Ca2+ influx through CaV1.3 channels initiates mitochondrial-Ca2+ (mito-Ca2+) uptake adjacent to ribbons. Block of mito-Ca2+ uptake in mature cells depresses presynaptic-Ca2+ influx and impacts synapse integrity. In developing zebrafish hair cells, mito-Ca2+ uptake coincides with spontaneous rises in presynaptic-Ca2+ influx. Spontaneous mito-Ca2+ loading lowers cellular NAD+/NADH redox and downregulates ribbon size. Direct application of NAD+ or NADH increases or decreases ribbon size respectively, possibly acting through the NAD(H)-binding domain on Ribeye. Our results present a mechanism where presynaptic- and mito-Ca2+ couple to confer proper presynaptic function and formation.

scholarly journals Synaptic mitochondria are critical for hair-cell synapse formation and function

2019 ◽  
Author(s):  
Hiu-tung C. Wong ◽  
Qiuxiang Zhang ◽  
Alisha J. Beirl ◽  
Ronald S. Petralia ◽  
Ya-Xian Wang ◽  
...  
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
Synapse Formation ◽  
Direct Application ◽  
Structural Protein ◽  
Ribbon Synapses ◽  
Presynaptic Function ◽  
Sensory Hair Cells ◽  
And Function ◽  
Cell Synapse

SummarySensory hair cells in the ear utilize specialized ribbon synapses. These synapses are defined by electron-dense presynaptic structures called ribbons, composed primarily of the structural protein Ribeye. Previous work has shown that voltage-gated influx of Ca2+through CaV1.3 channels is critical for hair-cell synapse function and can impede ribbon formation. We show that in mature zebrafish hair cells, evoked presynaptic-Ca2+influx through CaV1.3 channels initiates mitochondrial-Ca2+(mito-Ca2+) uptake adjacent to ribbons. Block of mito-Ca2+uptake in mature cells depresses presynaptic Ca2+influx and impacts synapse integrity. In developing zebrafish hair cells, mito-Ca2+uptake coincides with spontaneous rises in presynaptic Ca2+influx. Spontaneous mito-Ca2+loading lowers cellular NAD+/NADH redox and downregulates ribbon formation. Direct application of NAD+or NADH increases or decreases ribbon formation respectively, possibly acting through the NAD(H)-binding domain on Ribeye. Our results present a mechanism where presynaptic- and mito-Ca2+couple to confer proper presynaptic function and formation.

scholarly journals Common and rare genetic variants that could contribute to severe otitis media in an Australian Aboriginal population

2021 ◽  
Author(s):  
Sarra E Jamieson ◽  
Michaela Fakiola ◽  
Dave Tang ◽  
Elizabeth Scaman ◽  
Genevieve Syn ◽  
...  
Keyword(s):  
Hair Cell ◽  
Otitis Media ◽  
Genetic Risk ◽  
Transforming Growth Factor ◽  
Rare Variants ◽  
Protein Coding ◽  
Gene Sets ◽  
Growth Factor Signalling ◽  
Rare Genetic Variants ◽  
And Function

Abstract Background Our goal was to identify genetic risk factors for severe otitis media (OM) in Aboriginal Australians. Methods Illumina ® Omni2.5 BeadChip and imputed data were compared between 21 children with severe OM (multiple episodes chronic suppurative OM and/or perforations or tympanic sclerosis) and 370 individuals without this phenotype, followed by FUnctional Mapping and Annotation (FUMA). Exome data filtered for common (EXaC_all≥0.1) putative deleterious variants influencing protein coding (CADD-scaled scores ≥ 15) were used to compare 15 severe OM cases with 9 mild cases (single episode of acute OM recorded over ≥ 3 consecutive years). Rare (ExAC_all≤0.01) such variants were filtered for those present only in severe OM. Enrichr was used to determine enrichment of genes contributing to pathways/processes relevant to OM. Results FUMA analysis identified two plausible genetic risk loci for severe OM: NR3C1 (Pimputed_1000G=3.62x10 -6) encoding the glucocorticoid receptor, and NREP (Pimputed_1000G=3.67x10 -6) encoding neuronal regeneration related protein. Exome analysis showed: (i) association of severe OM with variants influencing protein coding (CADD-scaled ≥ 15) in a gene-set (GRXCR1, CDH23, LRP2, FAT4, ARSA, EYA4) enriched for Mammalian Phenotype Level 4 abnormal hair cell stereociliary bundle morphology and related phenotypes; (ii) rare variants influencing protein coding only seen in severe OM provided gene-sets enriched for “abnormal ear” (LMNA, CDH23, LRP2, MYO7A, FGFR1), integrin interactions, transforming growth factor signalling, and cell projection phenotypes including hair cell stereociliary bundles and cilium assembly. Conclusions This study highlights interacting genes and pathways related to cilium structure and function that may contribute to extreme susceptibility to OM in Aboriginal Australian children.

scholarly journals Fast Ca 2+ signals at mouse inner hair cell synapse: a role for Ca 2+ ‐induced Ca 2+ release

2002 ◽  
Vol 539 (1) ◽  
pp. 15-23 ◽  
Author(s):  
Helen J. Kennedy ◽  
Robert W. Meech
Keyword(s):  
Hair Cell ◽  
Inner Hair Cell ◽  
Cell Synapse

Shaker-1 mutations reveal roles for myosin VIIA in both development and function of cochlear hair cells

Development ◽  
1998 ◽  
Vol 125 (4) ◽  
pp. 557-566 ◽  
Author(s):  
T. Self ◽  
M. Mahony ◽  
J. Fleming ◽  
J. Walsh ◽  
S.D. Brown ◽  
...  
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
Usher Syndrome ◽  
Orthologous Gene ◽  
Cell Development ◽  
Cochlear Hair Cells ◽  
Cochlear Hair Cell ◽  
Show Evidence ◽  
Myosin Viia ◽  
And Function

The mouse shaker-1 locus, Myo7a, encodes myosin VIIA and mutations in the orthologous gene in humans cause Usher syndrome type 1B or non-syndromic deafness. Myo7a is expressed very early in sensory hair cell development in the inner ear. We describe the effects of three mutations on cochlear hair cell development and function. In the Myo7a816SB and Myo7a6J mutants, stereocilia grow and form rows of graded heights as normal, but the bundles become progressively more disorganised. Most of these mutants show no gross electrophysiological responses, but some did show evidence of hair cell depolarisation despite the disorganisation of their bundles. In contrast, the original shaker-1 mutants, Myo7ash1, had normal early development of stereocilia bundles, but still showed abnormal cochlear responses. These findings suggest that myosin VIIA is required for normal stereocilia bundle organisation and has a role in the function of cochlear hair cells.

scholarly journals Author response to letter to editor: Hyperinsulinemia adversely affects lung structure and function

2016 ◽  
Vol 311 (1) ◽  
pp. L183-L184 ◽  
Author(s):  
Suchita Singh ◽  
Manish Bodas ◽  
Naveen K. Bhatraju ◽  
Bijay Pattnaik ◽  
Atish Gheware ◽  
...  
Keyword(s):  
Structure And Function ◽  
Author Response ◽  
Lung Structure ◽  
And Function
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