Wnt signaling recruits KIF2A to the spindle to ensure chromosome congression and alignment during mitosis

被引：17

作者：

Bufe, Anja ^{[1
]}

Arco, Ana Garcia del ^{[1
]}

Hennecke, Magdalena ^{[2
,3
]}

de Jaime-Soguero, Anchel ^{[1
]}

Ostermaier, Matthias ^{[4
]}

Lin, Yu-Chih ^{[2
,3
]}

Ciprianidis, Anja ^{[1
]}

Hattemer, Janina ^{[1
]}

Engel, Ulrike ^{[1
,5
]}

Beli, Petra ^{[6
]}

Bastians, Holger ^{[2
,3
]}

Acebron, Sergio P. ^{[1
]}

机构：

[1] Heidelberg Univ, Ctr Organismal Studies, D-69120 Heidelberg, Germany

[2] Georg August Univ Gottingen, Sect Cellular Oncol, Inst Mol Oncol, Gottingen Ctr Mol Biosci, D-37077 Gottingen, Germany

[3] Georg August Univ Gottingen, Univ Med Ctr Gottingen, D-37077 Gottingen, Germany

[4] Inst Mol Biol IMB, D-55128 Mainz, Germany

[5] Heidelberg Univ, Nikon Imaging Ctr, Bioquant, D-69120 Heidelberg, Germany

[6] Johannes Gutenberg Univ Mainz, Inst Dev Biol & Neurobiol IDN, D-55128 Mainz, Germany

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2021年 / 118卷 / 34期

关键词：

Wnt signaling; mitosis; Dishevelled; chromosome alignment; Kinesin-13; CELL-DIVISION; BETA-CATENIN; PROTEIN STABILIZATION; MITOTIC SPINDLE; RECEPTOR; PHOSPHORYLATION; INSTABILITY; LRP6; DIFFERENTIATION; SEQUESTRATION;

D O I：

10.1073/pnas.2108145118

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Canonical Wnt signaling plays critical roles in development and tissue renewal by regulating beta-catenin target genes. Recent evidence showed that beta-catenin-independent Wnt signaling is also required for faithful execution of mitosis. However, the targets and specific functions of mitotic Wnt signaling still remain uncharacterized. Using phosphoproteomics, we identified that Wnt signaling regulates the microtubule depolymerase KIF2A during mitosis. We found that Dishevelled recruits KIF2A via its N-terminal and motor domains, which is further promoted upon LRP6 signalosome formation during cell division. We show that Wnt signaling modulates KIF2A interaction with PLK1, which is critical for KIF2A localization at the spindle. Accordingly, inhibition of basal Wnt signaling leads to chromosome misalignment in somatic cells and pluripotent stem cells. We propose that Wnt signaling monitors KIF2A activity at the spindle poles during mitosis to ensure timely chromosome alignment. Our findings highlight a function of Wnt signaling during cell division, which could have important implications for genome maintenance, notably in stem cells.

引用

页数：11

共 80 条

[1] beta-catenin is a target for the ubiquitin-proteasome pathway [J].