PUBLICATION

Rack1 is required for Vangl2 membrane localization and planar cell polarity signaling while attenuating canonical Wnt activity

Authors

Li, S., Esterberg, R., Lachance, V., Ren, D., Radde-Gallwitz, K., Chi, F., Parent, J.L., Fritz, A., and Chen, P.

ID

ZDB-PUB-110131-13

Date

2011

Source

Proceedings of the National Academy of Sciences of the United States of America 108(6): 2264-2269 (Journal)

Registered Authors

Fritz, Andreas

Keywords

none

MeSH Terms

Membrane Proteins/genetics
Membrane Proteins/metabolism*
Zebrafish/embryology*
Zebrafish/genetics
Mice
Protein Transport/physiology
Receptors, Cell Surface/genetics
Receptors, Cell Surface/metabolism*
Zebrafish Proteins/genetics
Zebrafish Proteins/metabolism*
Gastrulation/physiology*
Cell Division/physiology
Signal Transduction/physiology*
Wnt Proteins/genetics
Wnt Proteins/metabolism*
Gastrula/cytology
Gastrula/metabolism*
Protein Structure, Tertiary
Animals
Cell Polarity/physiology*
Cell Membrane/genetics
Cell Membrane/metabolism

(all 22)

PubMed

21262816 Full text @ Proc. Natl. Acad. Sci. USA

Abstract

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.

Genes / Markers

Figures

Show all Figures

Expression

Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT + MO1-vangl2	standard conditions	30%-epiboly	convergent extension involved in gastrulation disrupted, abnormal	Fig. 4
WT + MO1-vangl2	standard conditions	Shield	convergent extension involved in gastrulation disrupted, abnormal	Fig. 4
WT + MO1-vangl2	standard conditions	75%-epiboly	convergent extension involved in gastrulation disrupted, abnormal	Fig. 4
WT + MO1-vangl2	standard conditions	Bud	establishment of cell polarity disrupted, abnormal	Fig. 3
WT + MO1-vangl2	standard conditions	Bud	notochord increased width, abnormal	Fig. 3
WT + MO1-vangl2	standard conditions	Bud	notochord undulate, abnormal	Fig. 3
WT + MO1-vangl2	standard conditions	5-9 somites to 10-13 somites	notochord undulate, abnormal	Fig. 2
WT + MO1-vangl2	standard conditions	5-9 somites to 10-13 somites	somite increased width, abnormal	Fig. 2
WT + MO1-vangl2	standard conditions	5-9 somites to 10-13 somites	whole organism decreased length, abnormal	Fig. 2
WT + MO1-vangl2 + MO3-rack1	standard conditions	5-9 somites to 10-13 somites	notochord undulate, abnormal	Fig. 2

1 - 10 of 22

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Mutations / Transgenics

Human Disease / Model

Sequence Targeting Reagents

Fish

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
GFP	EFG	GFP

Mapping

Li et al., 2011 ZDB-PUB-110131-13 PMID:21262816

Rack1 is required for Vangl2 membrane localization and planar cell polarity signaling while attenuating canonical Wnt activity

Li et al., 2011

ZDB-PUB-110131-13
PMID:21262816