Inhibitory G proteins play multiple roles to polarize sensory hair cell morphogenesis DOI Open Access
Amandine Jarysta, Abigail L. D. Tadenev, Matthew Day

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: May 25, 2023

Inhibitory G alpha (GNAI or Gαi) proteins are critical for the polarized morphogenesis of sensory hair cells and hearing. The extent nature their actual contributions remains unclear, however, as previous studies did not investigate all GNAI included non-physiological approaches. Pertussis toxin can downregulate functionally redundant GNAI1, GNAI2, GNAI3 GNAO proteins, but may also induce unrelated defects. Here we directly systematically determine role(s) each individual protein in mouse auditory cells. GNAI2 similarly at cell apex with binding partner GPSM2, whereas GNAI1 detected. In

Language: Английский

Inhibitory G proteins play multiple roles to polarize sensory hair cell morphogenesis DOI Creative Commons
Amandine Jarysta, Abigail L. D. Tadenev, Matthew Day

et al.

eLife, Journal Year: 2023, Volume and Issue: 12

Published: July 18, 2023

Inhibitory G alpha (GNAI or Gαi) proteins are critical for the polarized morphogenesis of sensory hair cells and hearing. The extent nature their actual contributions remains unclear, however, as previous studies did not investigate all GNAI included non-physiological approaches. Pertussis toxin can downregulate functionally redundant GNAI1, GNAI2, GNAI3, GNAO proteins, but may also induce unrelated defects. Here, we directly systematically determine role(s) each individual protein in mouse auditory cells. GNAI2 GNAI3 similarly at cell apex with binding partner signaling modulator 2 (GPSM2), whereas GNAI1 detected. In Gnai3 mutants, progressively fails to fully occupy sub-cellular compartments where is missing. contrast, compensate loss essential bundle function. Simultaneous inactivation Gnai2 recapitulates first time two distinct types defects only observed so far pertussis toxin: (1) a delay failure basal body migrate off-center prospective cells, (2) reversal orientation some types. We conclude that break planar symmetry orient properly before GNAI2/3 regulate GPSM2.

Language: Английский

Citations

6
Inhibitory G proteins play multiple roles to polarize sensory hair cell morphogenesis DOI Creative Commons
Amandine Jarysta, Abigail L. D. Tadenev, Matthew Day

et al.

eLife, Journal Year: 2024, Volume and Issue: 12

Published: April 23, 2024

Inhibitory G alpha (GNAI or Gαi) proteins are critical for the polarized morphogenesis of sensory hair cells and hearing. The extent nature their actual contributions remains unclear, however, as previous studies did not investigate all GNAI included non-physiological approaches. Pertussis toxin can downregulate functionally redundant GNAI1, GNAI2, GNAI3, GNAO proteins, but may also induce unrelated defects. Here, we directly systematically determine role(s) each individual protein in mouse auditory cells. GNAI2 GNAI3 similarly at cell apex with binding partner signaling modulator 2 (GPSM2), whereas GNAI1 detected. In Gnai3 mutants, progressively fails to fully occupy sub-cellular compartments where is missing. contrast, compensate loss essential bundle function. Simultaneous inactivation Gnai2 recapitulates first time two distinct types defects only observed so far pertussis toxin: (1) a delay failure basal body migrate off-center prospective cells, (2) reversal orientation some types. We conclude that break planar symmetry orient properly before GNAI2/3 regulate GPSM2.

Language: Английский

Citations

1
Myosin XVA isoforms participate in the mechanotransduction-dependent remodeling of the actin cytoskeleton in auditory stereocilia DOI Creative Commons
Ana I. López-Porras, Ava M. Kruse,

Mark McClendon

et al.

Frontiers in Neurology, Journal Year: 2024, Volume and Issue: 15

Published: Dec. 23, 2024

Auditory hair cells form precise and sensitive staircase-like actin protrusions known as stereocilia. These specialized microvilli detect deflections induced by sound through the activation of mechano-electrical transduction (MET) channels located at their tips. At rest, a small MET channel current results in constant calcium influx which regulates morphology cytoskeleton shorter ‘transducing’ However, molecular mechanisms involved this novel type activity-driven plasticity stereocilium are currently unknown. Here, we tested contribution myosin XVA (MYO15A) isoforms, given roles regulation stereocilia dimensions during bundle development maintenance transducing mature cells. We used electron microscopy to evaluate morphological changes auditory cell after pharmacological blockage resting currents cochlear explants from mice that lacked one or all isoforms MYO15A. Hair lacking functional MYO15A did not exhibit MET-dependent remodeling cytoskeleton. In contrast, only long isoform exhibited increased remodeling, including tallest ‘non-transducing’ row bundle. conclude both enable fine-tune stereocilia, while also contributing stability row.

Language: Английский

Citations

1
Initiation and Formation of Stereocilia during the Development of Mouse Cochlear Hair Cells DOI Creative Commons
Suraj Ranganath Chakravarthy, Thomas S. van Zanten, Raj K. Ladher

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 27, 2024

ABSTRACT Stereocilia are apically located actin-protrusions found on the hair cells of inner ear. At least three rows stereocilia arranged in a graded staircase pattern, which is vital for mechanosensation. form soon after specification cells. While these steps have been well-characterized avian auditory epithelium, equivalent information mice lacking. Using scanning electron microscopy and super-resolution microscopy, we investigate formation from cell stages mouse organ Corti. Even before differentiation, find that sensory progenitors, will give rise to both support cells, dense lawn microvilli. Hair specialisation first apparent as an enrichment junctional actin, followed by relocalisation kinocilium into eccentric position thickening microvilli closest kinocilium. To determine actin signatures associated with development, use new analytical method map cellular filament distribution during development. By nomalising relative density, obtain insights cuticular plate development redistribution earliest phases specialisation.

Language: Английский

Citations

1
Spontaneous calcium transients in hair cell stereocilia DOI Creative Commons
Saman Hussain,

Miloslav Sedlacek,

Runjia Cui

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 13, 2024

Abstract The hair bundle of auditory and vestibular cells converts mechanical stimuli into electrical signals through mechanoelectrical transduction (MET). MET apparatus is built around a tip link that connects neighboring stereocilia are aligned in the direction mechanosensitivity bundle. Upon stimulation, channel complex responds to changes tip-link tension allows cation influx cell. Ca 2+ has been used as signature activity. Using genetically encoded sensors (GCaMP3, GCaMP6s) high-performance fluorescence confocal microscopy, we detect spontaneous transients individual developing fully formed bundles. We demonstrate this activity abolished by blockers thus likely originates from putative channels. observe mice tissue explants well vivo zebrafish cells, indicating functionally conserved. Within stereocilia, origin not limited canonical site at but also present along length. Remarkably, these microvilli-like structures on cell surface early stages development, prior onset MET. tallest rows traditionally thought contain hypothesize newly described may reflect stochastic opening. Localization other regions indicates presence pool channels or precursors. Our work provides insights assembly, maturation, function, turnover.

Language: Английский

Citations

1
Osteocyte Dendrites: How Do They Grow, Mature, and Degenerate in Mineralized Bone? DOI

Rosa M. Guerra,

Velia M. Fowler, Liyun Wang

et al.

Cytoskeleton, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 9, 2024

ABSTRACT Osteocytes, the most abundant bone cells, form an extensive cellular network via interconnecting dendrites. Like neurons in brain, long‐lived osteocytes perceive mechanical and biological inputs signal to other effector leading homeostasis turnover of tissues. Despite appreciation osteocytes' vital roles biology, initiation, growth, maintenance, eventual degradation osteocyte dendrites are poorly understood due their full encasement by mineralized matrix. With advancement imaging modalities genetic models, architectural organization molecular composition dendrites, as well morphological changes with aging diseases, have begun be revealed. However, several long‐standing mysteries remain unsolved, including (1) how initiated elongated when a surface osteoblast becomes embedded osteocyte; (2) maintain relatively stable morphology during decades‐long life span; (3) what processes control dendrite morphology, connectivity, stability; (4) if these influenced age, sex, hormones, loading. Our review long, thin actin filament (F‐actin)‐containing extending from cells leads working model that serves starting point investigate formation maintenance diseases.

Language: Английский

Citations

1
Spontaneous allelic variant in deafness–blindness gene Ush1g resulting in an expanded phenotype DOI Creative Commons
Vladimir L. Vartanian, Jocelyn F. Krey,

Paroma Chatterjee

et al.

Genes Brain & Behavior, Journal Year: 2023, Volume and Issue: 22(4)

Published: June 16, 2023

Abstract Relationships between novel phenotypic behaviors and specific genetic alterations are often discovered using target‐specific, directed mutagenesis or selection following chemical mutagenesis. An alternative approach is to exploit deficiencies in DNA repair pathways that maintain integrity response spontaneously induced damage. Mice deficient the glycosylase NEIL1 show elevated spontaneous mutations, which arise from translesion synthesis past oxidatively base Several litters of Neil1 knockout mice included animals were distinguished by their backwards‐walking behavior open‐field environments, while maintaining frantic forward movements home cage environment. Other manifestations swim test failures, head tilting circling. Mapping mutation conferred these showed introduction a stop codon at amino acid 4 Ush1g gene. bw/bw null displayed auditory vestibular defects commonly seen with mutations affecting inner‐ear hair‐cell function, including complete lack brainstem responses vestibular‐evoked potentials. As other Usher syndrome type I mutant mouse lines, hair cell phenotypes disorganized split bundles, as well altered distribution proteins for stereocilia localize tips row 1 2. Disruption bundle kinocilium displacement suggested USH1G essential forming cell's kinocilial links. Consistent models, had no substantial retinal degeneration compared bw /+ controls. In contrast previously described alleles, this new allele provides first model

Language: Английский

Citations

3
Inhibitory G proteins play multiple roles to polarize sensory hair cell morphogenesis DOI Open Access
Amandine Jarysta, Abigail L. D. Tadenev, Matthew Day

et al.

Published: April 4, 2024

Inhibitory G alpha (GNAI or Gαi) proteins are critical for the polarized morphogenesis of sensory hair cells and hearing. The extent nature their actual contributions remains unclear, however, as previous studies did not investigate all GNAI included non-physiological approaches. Pertussis toxin can downregulate functionally redundant GNAI1, GNAI2, GNAI3 GNAO proteins, but may also induce unrelated defects. Here we directly systematically determine role(s) each individual protein in mouse auditory cells. GNAI2 similarly at cell apex with binding partner GPSM2, whereas GNAI1 detected. In Gnai3 mutants, progressively fails to fully occupy subcellular compartments where is missing. contrast, compensate loss essential bundle function. Simultaneous inactivation Gnai2 recapitulates first time two distinct types defects only observed so far pertussis toxin: 1) a delay failure basal body migrate off-center prospective cells, 2) reversal orientation some types. We conclude that break planar symmetry orient properly before GNAI2/3 regulate GPSM2.

Language: Английский

Citations

0
Myosin XVA isoforms participate in the mechanotransduction-dependent remodeling of the actin cytoskeleton in auditory stereocilia DOI
Ana I. López-Porras, Ava M. Kruse,

Mark McClendon

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 7, 2024

Auditory hair cells form precise and sensitive staircase-like actin protrusions known as stereocilia. These specialized microvilli detect deflections induced by sound through the activation of mechano-electrical transduction (MET) channels located at their tips. At rest, a small MET channel current results in constant calcium influx, which regulates morphology cytoskeleton shorter 'transducing' However, molecular mechanisms involved this novel type activity-driven plasticity stereocilium are currently unknown. Here, we tested contribution myosin XVA (MYO15A) isoforms. We used electron microscopy to evaluate morphological changes auditory cell stereocilia after pharmacological blockage resting currents cochlear explants from mice that lacked one or all isoforms MYO15A. Hair lacking functional MYO15A did not exhibit MET-dependent remodeling cytoskeleton. In contrast, only lack long isoform exhibited increased remodeling, including tallest 'non-transducing' row bundle. conclude enable but also fine-tune transducing contribute stability row.

Language: Английский

Citations

0
Development of the mouse inner ear DOI
Doris K. Wu, Karen P. Steel, Linda J. Sandell

et al.

Elsevier eBooks, Journal Year: 2024, Volume and Issue: unknown, P. 405 - 419

Published: Dec. 4, 2024

Language: Английский

Citations

0