2015
DOI: 10.7554/elife.07091
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Daple is a novel non-receptor GEF required for trimeric G protein activation in Wnt signaling

Abstract: Wnt signaling is essential for tissue homeostasis and its dysregulation causes cancer. Wnt ligands trigger signaling by activating Frizzled receptors (FZDRs), which belong to the G-protein coupled receptor superfamily. However, the mechanisms of G protein activation in Wnt signaling remain controversial. In this study, we demonstrate that FZDRs activate G proteins and trigger non-canonical Wnt signaling via the Dishevelled-binding protein, Daple. Daple contains a Gα-binding and activating (GBA) motif, which ac… Show more

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Cited by 127 publications

(367 citation statements)
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“…Consistent with published studies ( Aznar et al, 2015 ), our findings suggest a model in which Wnts activate Gαi proteins through membrane recruitment of Daple. In turn, free Gβγ activates PI3K to couple kinocilium positioning with hair bundle orientation and to localize a subset of core PCP proteins, thereby coordinating iPCP and PCP in the OC ( Fig.…”
Section: Resultssupporting
confidence: 93%
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.
“…Consistent with published studies ( Aznar et al, 2015 ), our findings suggest a model in which Wnts activate Gαi proteins through membrane recruitment of Daple. In turn, free Gβγ activates PI3K to couple kinocilium positioning with hair bundle orientation and to localize a subset of core PCP proteins, thereby coordinating iPCP and PCP in the OC ( Fig.…”
Section: Resultssupporting
confidence: 93%
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.
“…Fluorescently-labeled GIV-derived peptides would be expected to yield an increase of FP upon binding to Gαi3 (~40 KDa). We found that the longest peptide (GIV 1671–1705) bound Gαi3 with K d of ~0.5 µM, which is in agreement with the affinity of larger GIV fragments reported previously using pulldown assays 49 , 51 . Binding of GIV 1671–1701 was indistinguishable from GIV 1671–1705, whereas the shorter GIV 1671–1696 peptide showed slightly diminished affinity (K d ~0.65 µM) (Fig.…”
Section: Resultssupporting
confidence: 91%
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.
“…We speculate that the prometastatic trends we observed in the case of both Daple-V1 and S100A4 did not reach significance because of insufficient patients in the cohort. Regardless, these findings are consistent with our recent findings that Daple-V2 is a potent tumor suppressor, whereas Daple-V1 triggers EMT and invasion 18,22 .
Figure 5Frequency of progression to metastasis among patients stratified based on high vs . low levels of circulating transcripts of Daple-V2 alone ( A ), Daple-V1 alone ( B ), Daple V1 and V2 combined ( C ), and S100A4 ( D ) in the peripheral blood.
…”
Section: Resultssupporting
confidence: 91%
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.