Wnts regulate planar cell polarity via heterotrimeric G protein and PI3K signaling

Malt, André Landin; Hogan, Arielle; Smith, Connor D.; Madani, Maxwell S.; Lu, Xiaowei

doi:10.1083/jcb.201912071

Journal of Cell Biology

2020

DOI: 10.1083/jcb.201912071

|Get access via publisher |Summarize |Cite

|

Sign up to set email alerts

Wnts regulate planar cell polarity via heterotrimeric G protein and PI3K signaling

André Landin Malt

¹

,

Arielle Hogan

²

,

Connor D. Smith

³

et al.

Abstract: In the mammalian cochlea, the planar cell polarity (PCP) pathway aligns hair cell orientation along the plane of the sensory epithelium. Concurrently, multiple cell intrinsic planar polarity (referred to as iPCP) modules mediate planar polarization of the hair cell apical cytoskeleton, including the kinocilium and the V-shaped hair bundle essential for mechanotransduction. How PCP and iPCP are coordinated during development and the roles of Wnt ligands in this process remain unresolved. Here we show that genet… Show more

Help me understand this report

Cited by 24 publications

(27 citation statements)

References 56 publications

Supporting

2

Mentioning

25

Contrasting

0

Unclassified

0

Order By: Relevance

“…Here, we have used two independent transgenic mouse models to prevent Wnt secretion in the cochlear duct, and found that Wnt secretion is required for planar polarization of sensory HCs. Similar results were independently reported recently (Landin Malt et al, 2020). Although the severity of PCP defects was mild, using asymmetric localization of PCP proteins as a molecular read out, we revealed specific PCP proteins that lost asymmetry in HCs in the Wls cKO cochlea.…”

Section: Discussionsupporting

confidence: 91%

Dual regulation of planar polarization by secreted Wnts and Vangl2 in the developing mouse cochlea

Najarro

¹

,

Huang

²

,

Jacobo

³

et al. 2020

Get access via publisher Add to dashboard Cite

Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

show abstract

“…Here, we have used two independent transgenic mouse models to prevent Wnt secretion in the cochlear duct, and found that Wnt secretion is required for planar polarization of sensory HCs. Similar results were independently reported recently (Landin Malt et al, 2020). Although the severity of PCP defects was mild, using asymmetric localization of PCP proteins as a molecular read out, we revealed specific PCP proteins that lost asymmetry in HCs in the Wls cKO cochlea.…”

Section: Discussionsupporting

confidence: 91%

Dual regulation of planar polarization by secreted Wnts and Vangl2 in the developing mouse cochlea

Najarro

¹

,

Huang

²

,

Jacobo

³

et al. 2020

Get access via publisher Add to dashboard Cite

Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

show abstract

“…Similar iPCP defects were observed in Wls cKO and Rac1deficient cochleae, including misoriented and misshapen hair bundles with an off-center kinocilium (Grimsley-Myers et al, 2009;Landin Malt et al, 2020), consistent with Rac1 being a downstream effector of Wnt-regulated hair bundle polarity. To test this, we examined hair bundle orientation and kinocilium positioning in Wls cKO ; Rac1DA/+ cochleae at E18.5.…”

Section: Effects Of Rac1 Activation On Hair Bundle Defects Of Wls Ckosupporting

confidence: 66%

“…We next assessed the effect of Rac1 activation on kinocilium positioning within the hair bundle by measuring the kinocilium index (Landin Malt et al, 2020). In the wild type at E18.5, the kinocilium is found at the vertex of the V-shaped hair bundle, with a mean kinocilium index (KI) of 1.16, whereas many hair bundles in Wls cKO cochleae had an off-center kinocilium, as shown previously (Figures 4A,D, arrows).…”

Section: Effects Of Rac1 Activation On Hair Bundle Defects Of Wls Ckomentioning

confidence: 64%

“…We and others previously uncovered a requirement of secreted Wnt ligands in asymmetric junctional localization of a subset of core PCP proteins (Landin Malt et al, 2020;Najarro et al, 2020). Specifically, Fzd6 is normally enriched along the medial border of HCs (Figures 5A,B, arrows, 7A), and this localization was abolished in the Wls cKO cochleae (Figures 5G,H, 7D).…”

Section: Rac1 Activation and Gsk3β Inactivationmentioning

confidence: 76%

See 1 more Smart Citation

Non-Canonical Wnt Signaling Regulates Cochlear Outgrowth and Planar Cell Polarity via Gsk3β Inhibition

Malt

¹

,

Clancy

²

,

Hwang

³

et al. 2021

Front. Cell Dev. Biol.

Self Cite

Get access via publisher Add to dashboard Cite

Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

show abstract

“…We propose that GPR156 acts as a conventional GPCR with Guanine nucleotide Exchange Factor (GEF) activity to activate the heterotrimeric Gαiβγ complex and direct HC reversal. HC reversal is probably signaled by Gαi-GTP, as inhibiting Gβγ pharmacologically did not invert OHC orientation in vitro 55 . Remarkably, Gpsm2 and Gpr156 mutants have no phenotype in common (Fig.…”

Section: Discussionmentioning

confidence: 94%

EMX2-GPR156-Gαi reverses hair cell orientation in mechanosensory epithelia

Kindt

¹

,

Aktürk

²

,

Jarysta

³

et al. 2021

Get access via publisher Add to dashboard Cite

Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

show abstract

Scite is an AI-powered platform that helps researchers discover and evaluate scientific literature through Smart Citations, showing whether studies support or contradict a claim. Now part of Research Solutions, Scite has indexed 1.6B+ citations, partners with 30+ publishers, and serves 2M users worldwide.

Contact Info

customersupport@researchsolutions.com

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA