Rack1 is required for Vangl2 membrane localization and planar cell polarity signaling while attenuating canonical Wnt activity.
The vertebrate planar cell polarity (PCP) pathway shares molecular components with the β-catenin-mediated canonical Wnt pathway but acts through membrane complexes containing Vang or Frizzled to orient neighboring cells coordinately. The molecular interactions underlying the action of Vang in PCP signaling and specification, however, are yet to be delineated. Here, we report the identification of Rack1 as an interacting protein of a vertebrate Vang protein, Vangl2. We demonstrate that Rack1 is required in zebrafish for PCP-regulated processes, including oriented cell division, cellular polarization, and convergent extension during gastrulation. We further show that the knockdown of Rack1 affects membrane localization of Vangl2 and that the Vangl2-interacting domain of Rack1 has a dominant-negative effect on Vangl2 localization and gastrulation. Moreover, Rack1 antagonizes canonical Wnt signaling. Together, our data suggest that Rack1 regulates the localization of an essential PCP protein and acts as a molecular switch to promote PCP signaling.
Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Shuangding
S
Li
Robert
R
Esterberg
Veronik
V
Lachance
Dongdong
D
Ren
Kristen
K
Radde-Gallwitz
Fanglu
F
Chi
Jean-Luc
JL
Parent
Andreas
A
Fritz
Ping
P
Chen
D000818:Animals; D002455:Cell Division / Q000502:physiology; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D016764:Cell Polarity / Q000502:physiology*; D005775:Gastrula / Q000166:cytology / Q000378:metabolism*; D054262:Gastrulation / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000502:physiology; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
D008565:Membrane Proteins; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; D051153:Wnt Proteins; D029961:Zebrafish Proteins; C491759:vangl2 protein, zebrafish
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