Open AccessPhase separation of Axin organizes the β-catenin destruction complex
Author(s) -
Junxiu g,
Kexin Kang,
Qiaoni Shi,
Xinhui Zhu,
Qinghua Tao,
Ye-Guang Chen
Publication year - 2021
Publication title -
the journal of cell biology/the journal of cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.414
H-Index - 380
eISSN - 1540-8140
pISSN - 0021-9525
DOI - 10.1083/jcb.202012112
Subject(s) - wnt signaling pathway , gsk 3 , casein kinase 1 , biology , adenomatous polyposis coli , microbiology and biotechnology , beta catenin , catenin , scaffold protein , multiprotein complex , phosphorylation , protein kinase a , signal transduction , biochemistry , genetics , colorectal cancer , cancer , gene
In Wnt/β-catenin signaling, the β-catenin protein level is deliberately controlled by the assembly of the multiprotein β-catenin destruction complex composed of Axin, adenomatous polyposis coli (APC), glycogen synthase kinase 3β (GSK3β), casein kinase 1α (CK1α), and others. Here we provide compelling evidence that formation of the destruction complex is driven by protein liquid–liquid phase separation (LLPS) of Axin. An intrinsically disordered region in Axin plays an important role in driving its LLPS. Phase-separated Axin provides a scaffold for recruiting GSK3β, CK1α, and β-catenin. APC also undergoes LLPS in vitro and enhances the size and dynamics of Axin phase droplets. The LLPS-driven assembly of the destruction complex facilitates β-catenin phosphorylation by GSK3β and is critical for the regulation of β-catenin protein stability and thus Wnt/β-catenin signaling.