YAP/TAZ-CDC42 signaling regulates vascular tip cell migration

Masahide Sakabe; Jieqing Fan; Yoshinobu Odaka; Ning Liu; Aishlin Hassan; Xin Duan; Paige Stump; Luke Byerly; Megan Donaldson; Jiukuan Hao; Marcus Fruttiger; Qing Richard Lu; Yi Zheng; Richard A. Lang; Mei Xin

doi:10.1073/pnas.1704030114

YAP/TAZ-CDC42 signaling regulates vascular tip cell migration

Masahide Sakabe, Jieqing Fan, Yoshinobu Odaka, Ning Liu, Aishlin Hassan, Xin Duan, Paige Stump, Luke Byerly, Megan Donaldson, Jiukuan Hao, Marcus Fruttiger, Qing Richard Lu, Yi Zheng, Richard A. Lang, Mei Xin

Research output: Contribution to journal › Article › peer-review

133 Scopus citations

Abstract

Angiogenesis and vascular remodeling are essential for the establishment of vascular networks during organogenesis. Here we show that the Hippo signaling pathway effectors YAP and TAZ are required, in a gene dosage-dependent manner, for the proliferation and migration of vascular endothelial cells (ECs) during retinal angiogenesis. Intriguingly, nuclear translocation of YAP and TAZ induced by Lats1/2-deletion blocked endothelial migration and phenocopied Yap/Taz-deficient mutants. Furthermore, overexpression of a cytoplasmic form of YAP (YAPS127D) partially rescued the migration defects caused by loss of YAP and TAZ function. Finally, we found that cytoplasmic YAP positively regulated the activity of the small GTPase CDC42, deletion of which caused severe defects in endothelial migration. These findings uncover a previously unrecognized role of cytoplasmic YAP/TAZ in promoting cell migration by activating CDC42 and provide insight into how Hippo signaling in ECs regulates angiogenesis.

Original language	English (US)
Pages (from-to)	10918-10923
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	114
Issue number	41
DOIs	https://doi.org/10.1073/pnas.1704030114
State	Published - Oct 10 2017

Keywords

Angiogenesis
CDC42
Cell migration
Hippo signaling

ASJC Scopus subject areas

General

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10.1073/pnas.1704030114

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Sakabe, M., Fan, J., Odaka, Y., Liu, N., Hassan, A., Duan, X., Stump, P., Byerly, L., Donaldson, M., Hao, J., Fruttiger, M., Lu, Q. R., Zheng, Y., Lang, R. A., & Xin, M. (2017). YAP/TAZ-CDC42 signaling regulates vascular tip cell migration. Proceedings of the National Academy of Sciences of the United States of America, 114(41), 10918-10923. https://doi.org/10.1073/pnas.1704030114

Sakabe, M, Fan, J, Odaka, Y, Liu, N, Hassan, A, Duan, X, Stump, P, Byerly, L, Donaldson, M, Hao, J, Fruttiger, M, Lu, QR, Zheng, Y, Lang, RA & Xin, M 2017, 'YAP/TAZ-CDC42 signaling regulates vascular tip cell migration', Proceedings of the National Academy of Sciences of the United States of America, vol. 114, no. 41, pp. 10918-10923. https://doi.org/10.1073/pnas.1704030114

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title = "YAP/TAZ-CDC42 signaling regulates vascular tip cell migration",

abstract = "Angiogenesis and vascular remodeling are essential for the establishment of vascular networks during organogenesis. Here we show that the Hippo signaling pathway effectors YAP and TAZ are required, in a gene dosage-dependent manner, for the proliferation and migration of vascular endothelial cells (ECs) during retinal angiogenesis. Intriguingly, nuclear translocation of YAP and TAZ induced by Lats1/2-deletion blocked endothelial migration and phenocopied Yap/Taz-deficient mutants. Furthermore, overexpression of a cytoplasmic form of YAP (YAPS127D) partially rescued the migration defects caused by loss of YAP and TAZ function. Finally, we found that cytoplasmic YAP positively regulated the activity of the small GTPase CDC42, deletion of which caused severe defects in endothelial migration. These findings uncover a previously unrecognized role of cytoplasmic YAP/TAZ in promoting cell migration by activating CDC42 and provide insight into how Hippo signaling in ECs regulates angiogenesis.",

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author = "Masahide Sakabe and Jieqing Fan and Yoshinobu Odaka and Ning Liu and Aishlin Hassan and Xin Duan and Paige Stump and Luke Byerly and Megan Donaldson and Jiukuan Hao and Marcus Fruttiger and Lu, {Qing Richard} and Yi Zheng and Lang, {Richard A.} and Mei Xin",

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doi = "10.1073/pnas.1704030114",

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T1 - YAP/TAZ-CDC42 signaling regulates vascular tip cell migration

AU - Sakabe, Masahide

AU - Fan, Jieqing

AU - Odaka, Yoshinobu

AU - Liu, Ning

AU - Hassan, Aishlin

AU - Duan, Xin

AU - Stump, Paige

AU - Byerly, Luke

AU - Donaldson, Megan

AU - Hao, Jiukuan

AU - Fruttiger, Marcus

AU - Lu, Qing Richard

AU - Zheng, Yi

AU - Lang, Richard A.

AU - Xin, Mei

PY - 2017/10/10

Y1 - 2017/10/10

N2 - Angiogenesis and vascular remodeling are essential for the establishment of vascular networks during organogenesis. Here we show that the Hippo signaling pathway effectors YAP and TAZ are required, in a gene dosage-dependent manner, for the proliferation and migration of vascular endothelial cells (ECs) during retinal angiogenesis. Intriguingly, nuclear translocation of YAP and TAZ induced by Lats1/2-deletion blocked endothelial migration and phenocopied Yap/Taz-deficient mutants. Furthermore, overexpression of a cytoplasmic form of YAP (YAPS127D) partially rescued the migration defects caused by loss of YAP and TAZ function. Finally, we found that cytoplasmic YAP positively regulated the activity of the small GTPase CDC42, deletion of which caused severe defects in endothelial migration. These findings uncover a previously unrecognized role of cytoplasmic YAP/TAZ in promoting cell migration by activating CDC42 and provide insight into how Hippo signaling in ECs regulates angiogenesis.

AB - Angiogenesis and vascular remodeling are essential for the establishment of vascular networks during organogenesis. Here we show that the Hippo signaling pathway effectors YAP and TAZ are required, in a gene dosage-dependent manner, for the proliferation and migration of vascular endothelial cells (ECs) during retinal angiogenesis. Intriguingly, nuclear translocation of YAP and TAZ induced by Lats1/2-deletion blocked endothelial migration and phenocopied Yap/Taz-deficient mutants. Furthermore, overexpression of a cytoplasmic form of YAP (YAPS127D) partially rescued the migration defects caused by loss of YAP and TAZ function. Finally, we found that cytoplasmic YAP positively regulated the activity of the small GTPase CDC42, deletion of which caused severe defects in endothelial migration. These findings uncover a previously unrecognized role of cytoplasmic YAP/TAZ in promoting cell migration by activating CDC42 and provide insight into how Hippo signaling in ECs regulates angiogenesis.

KW - Angiogenesis

KW - CDC42

KW - Cell migration

KW - Hippo signaling

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YAP/TAZ-CDC42 signaling regulates vascular tip cell migration

Abstract

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