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

Control of stereocilia length during development of hair bundles DOI Creative Commons
Jocelyn F. Krey,

Paroma Chatterjee,

Julia Halford

et al.

PLoS Biology, Journal Year: 2023, Volume and Issue: 21(4), P. e3001964 - e3001964

Published: April 3, 2023

Assembly of the hair bundle, sensory organelle inner ear, depends on differential growth actin-based stereocilia. Separate rows stereocilia, labeled 1 through 3 from tallest to shortest, lengthen or shorten during discrete time intervals development. We used lattice structured illumination microscopy and surface rendering measure dimensions stereocilia mouse apical cells early postnatal development; these measurements revealed a sharp transition at day 8 between stage III (row 2 widening; row shortening) IV (final lengthening widening). Tip proteins that determine did not accumulate simultaneously stages IV; while actin-bundling protein EPS8 peaked end III, GNAI3 several days later—in IV—and GPSM2 near IV. To establish contributions key macromolecular assemblies bundle structure, we examined mutants eliminated tip links ( Cdh23 v2J Pcdh15 av3J ), transduction channels Tmie KO complex Myo15a sh2 ). v2J/v2J av3J/av3J bundles had adjacent in same were matched length, revealing major role cadherins is synchronize lengths side-by-side Use tip-link also allowed us distinguish effects themselves. While levels GPSM2, which stimulate elongation, greatly attenuated tips KO/KO they accumulated normally These results reinforced suggestion themselves facilitate localization complex. By contrast, concentrates all , correlating with less polarized distribution bundles. latter indicated wild-type cells, prevents accumulation shorter causing them shrink (rows 3) disappear 4 microvilli). Reduced rhodamine-actin labeling suggests transduction’s destabilize actin filaments there. suggest regulation length occurs CDH23 PCDH15 regulate beyond their gating mechanotransduction channels.

Language: Английский

Citations

25
Heterotrimeric G protein signaling without GPCRs: The Gα-binding-and-activating (GBA) motif DOI Creative Commons
Mikel Garcia‐Marcos

Journal of Biological Chemistry, Journal Year: 2024, Volume and Issue: 300(3), P. 105756 - 105756

Published: Feb. 15, 2024

Heterotrimeric G proteins (Gαβγ) are molecular switches that relay signals from 7-transmembrane receptors located at the cell surface to cytoplasm. The function of these is so intimately linked heterotrimeric they named protein-coupled (GPCRs), showcasing interdependent nature this archetypical receptor-transducer axis transmembrane signaling in eukaryotes. It generally assumed activation protein occurs exclusively by action GPCRs, but idea has been challenged discovery alternative mechanisms which can propagate cell. This review will focus on a general principle operates without direct involvement GPCRs. mechanism reviewed here mediated class regulators defined containing an evolutionarily conserved sequence Gα-binding-and-activating (GBA) motif. Using best characterized with GBA motif as examples, Gα-interacting vesicle-associated (GIV)/Girdin and dishevelled-associating high frequency leucine residues (DAPLE), cover (i) extracellular cues not relayed GPCRs promote coupling motif-containing proteins, (ii) structural basis for how motifs interact Gα subunits facilitate signaling, (iii) relevance different cellular pathological processes, including cancer birth defects, (iv) strategies manipulate GBA-G experimental therapeutics purposes, development rationally engineered chemical probes.

Language: Английский

Citations

6
Not a hair out of place: Polarizing and orienting sensory hair cells DOI
Katie S. Kindt, Basile Tarchini

Current topics in developmental biology/Current Topics in Developmental Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
3D morphology of an outer-hair-cell hair bundle increases its displacement and dynamic range DOI

Zenghao Zhu,

Wisam Reid, Shefin Sam George

et al.

Biophysical Journal, Journal Year: 2024, Volume and Issue: 123(19), P. 3433 - 3451

Published: Aug. 19, 2024

Language: Английский

Citations

3
Mitochondrial gene SLC25A24 regulated anti-tumor immunity and inhibited the proliferation and metastasis of colorectal cancer by PKG1-dependent cGMP/PKG1 pathway DOI
Yan Gao, Yinghui Peng, Yulai Zhou

et al.

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 157, P. 114664 - 114664

Published: May 6, 2025

Language: Английский

Citations

0
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
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: 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 determined role(s) each individual protein in mouse auditory cells. GNAI2 similarly at cell apex with binding partner GPSM2, whereas GNAI1 neither detected nor polarized. 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

2
Control of stereocilia length during development of hair bundles DOI Creative Commons
Jocelyn F. Krey,

Paroma Chatterjee,

Julia Halford

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: Dec. 19, 2022

Abstract Assembly of the hair bundle, sensory organelle inner ear, depends on differential growth actin-based stereocilia. Separate rows stereocilia, labeled 1 through 3 from tallest to shortest, lengthen or shorten during discrete time intervals development. We used lattice structured illumination microscopy and surface rendering mouse apical cells measure stereocilia dimensions early postnatal development; these measurements revealed a sharp transition at day 8 between stage III (row 2 widening; row shortening) IV (final lengthening widening). Tip proteins that determine did not accumulate simultaneously stages IV; while actin-bundling protein EPS8 peaked end III, GNAI3 several days later—in IV—and GPSM2 near IV. To establish contributions key macromolecular assemblies bundle structure, we examined mutants eliminated tip links ( Cdh23 v2J Pcdh15 av3J ), transduction channels Tmie KO complex Myo15a sh2 ). v2J/v2J av3J/av3J bundles had adjacent in same were matched length, revealing major role cadherins is synchronize lengths side-by-side Use tip-link also allowed us distinguish effects themselves. While levels GPSM2, which stimulate elongation, greatly attenuated tips KO/KO they accumulated normally These results reinforced suggestion themselves facilitate localization complex. By contrast, concentrates all , correlating with less polarized distribution bundles. latter indicated wild-type cells, prevents accumulation shorter causing them shrink 3) disappear 4 microvilli). Reduced rhodamine-actin labeling suggests transduction’s destabilize actin filaments there. suggest regulation length occurs EPS8, CDH23 PCDH15 regulate beyond their gating mechanotransduction channels.

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