Click here to close Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly. We suggest using a current version of Chrome, FireFox, or Safari.
XB-ART-54411
Dev Cell January 1, 2018; 44 (2): 248-260.e4.

RAPGEF5 Regulates Nuclear Translocation of β-Catenin.

Griffin JN , Del Viso F , Duncan AR , Robson A , Hwang W , Kulkarni S , Liu KJ , Khokha MK .


Abstract
Canonical Wnt signaling coordinates many critical aspects of embryonic development, while dysregulated Wnt signaling contributes to common diseases, including congenital malformations and cancer. The nuclear localization of β-catenin is the defining step in pathway activation. However, despite intensive investigation, the mechanisms regulating β-catenin nuclear transport remain undefined. In a patient with congenital heart disease and heterotaxy, a disorder of left-right patterning, we previously identified the guanine nucleotide exchange factor, RAPGEF5. Here, we demonstrate that RAPGEF5 regulates left-right patterning via Wnt signaling. In particular, RAPGEF5 regulates the nuclear translocation of β-catenin independently of both β-catenin cytoplasmic stabilization and the importin β1/Ran-mediated transport system. We propose a model whereby RAPGEF5 activates the nuclear GTPases, Rap1a/b, to facilitate the nuclear transport of β-catenin, defining a parallel nuclear transport pathway to Ran. Our results suggest new targets for modulating Wnt signaling in disease states.

PubMed ID: 29290587
PMC ID: PMC5818985
Article link: Dev Cell
Grant support: [+]
Genes referenced: chrd.1 ctnnb1 dand5 fgf8 fgfr1op foxj1 foxj1.2 gdf3 gsc gsk3b lrp1 nodal nodal1 nodal3.1 nog not otx2 pitx2 ralgds ran rap1a rap1b rap2a rap2b rapgef5 rpe ventx1.1
Antibodies: Ctnnb1 Ab1 Ctnnb1 Ab2 H3f3a Ab33 Rap1a Ab1 Rap2a Ab1 Rapgef5 Ab1
Morpholinos: rapgef5 MO1 rapgef5 MO2


Article Images: [+] show captions
References:
Bhanot, 1996, Pubmed [+]


Xenbase: The Xenopus laevis and X. tropicalis resource.
Version: 4.11.3


Major funding for Xenbase is provided by grant P41 HD064556