Yes-associated protein impacts adherens junction assembly through regulating actin cytoskeleton organization

Haibo Bai, Qingfeng Zhu, Alexandra Surcel, Tianzhi Luo, Yixin Ren, Bin Guan, Ying Liu, Nan Wu, Nora Eve Joseph, Tian-Li Wang, Nailing Zhang, Duojia Pan, Gianfranco Alpini, Douglas Robinson, Robert A Anders

Research output: Contribution to journalArticle

Abstract

The Hippo pathway effector Yes-associated protein (YAP) regulates liver size by promoting cell proliferation and inhibiting apoptosis. However, recent in vivo studies suggest that YAP has important cellular functions other than controlling proliferation and apoptosis. Transgenic YAP expression in mouse hepatocytes results in severe jaundice. A possible explanation for the jaundice could be defects in adherens junctions that prevent bile from leaking into the blood stream. Indeed, immunostaining of E-cadherin and electron microscopic examination of bile canaliculi of Yap transgenic livers revealed abnormal adherens junction structures. Using primary hepatocytes from Yap transgenic livers and Yap knockout livers, we found that YAP antagonizes E-cadherin-mediated cell-cell junction assembly by regulating the cellular actin architecture, including its mechanical properties (elasticity and cortical tension). Mechanistically, we found that YAP promoted contractile actin structure formation by upregulating nonmuscle myosin light chain expression and cellular ATP generation. Thus, by modulating actomyosin organization, YAP may influence many actomyosin-dependent cellular characteristics, including adhesion, membrane protrusion, spreading, morphology, and cortical tension and elasticity, which in turn determine cell differentiation and tissue morphogenesis.

Original languageEnglish (US)
Pages (from-to)G396-G411
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume311
Issue number3
DOIs
StatePublished - 2016

Fingerprint

Adherens Junctions
Actin Cytoskeleton
Actomyosin
Liver
Elasticity
Cadherins
Jaundice
Proteins
Actins
Hepatocytes
Bile Canaliculi
Apoptosis
Contractile Proteins
Myosin Light Chains
Intercellular Junctions
Morphogenesis
Bile
Cell Differentiation
Adenosine Triphosphate
Cell Proliferation

Keywords

  • Actin cytoskeleton
  • Adherens junctions
  • YAP

ASJC Scopus subject areas

  • Physiology
  • Medicine(all)
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

Cite this

Yes-associated protein impacts adherens junction assembly through regulating actin cytoskeleton organization. / Bai, Haibo; Zhu, Qingfeng; Surcel, Alexandra; Luo, Tianzhi; Ren, Yixin; Guan, Bin; Liu, Ying; Wu, Nan; Joseph, Nora Eve; Wang, Tian-Li; Zhang, Nailing; Pan, Duojia; Alpini, Gianfranco; Robinson, Douglas; Anders, Robert A.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 311, No. 3, 2016, p. G396-G411.

Research output: Contribution to journalArticle

Bai, Haibo ; Zhu, Qingfeng ; Surcel, Alexandra ; Luo, Tianzhi ; Ren, Yixin ; Guan, Bin ; Liu, Ying ; Wu, Nan ; Joseph, Nora Eve ; Wang, Tian-Li ; Zhang, Nailing ; Pan, Duojia ; Alpini, Gianfranco ; Robinson, Douglas ; Anders, Robert A. / Yes-associated protein impacts adherens junction assembly through regulating actin cytoskeleton organization. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 2016 ; Vol. 311, No. 3. pp. G396-G411.
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AU - Zhu, Qingfeng

AU - Surcel, Alexandra

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AU - Ren, Yixin

AU - Guan, Bin

AU - Liu, Ying

AU - Wu, Nan

AU - Joseph, Nora Eve

AU - Wang, Tian-Li

AU - Zhang, Nailing

AU - Pan, Duojia

AU - Alpini, Gianfranco

AU - Robinson, Douglas

AU - Anders, Robert A

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N2 - The Hippo pathway effector Yes-associated protein (YAP) regulates liver size by promoting cell proliferation and inhibiting apoptosis. However, recent in vivo studies suggest that YAP has important cellular functions other than controlling proliferation and apoptosis. Transgenic YAP expression in mouse hepatocytes results in severe jaundice. A possible explanation for the jaundice could be defects in adherens junctions that prevent bile from leaking into the blood stream. Indeed, immunostaining of E-cadherin and electron microscopic examination of bile canaliculi of Yap transgenic livers revealed abnormal adherens junction structures. Using primary hepatocytes from Yap transgenic livers and Yap knockout livers, we found that YAP antagonizes E-cadherin-mediated cell-cell junction assembly by regulating the cellular actin architecture, including its mechanical properties (elasticity and cortical tension). Mechanistically, we found that YAP promoted contractile actin structure formation by upregulating nonmuscle myosin light chain expression and cellular ATP generation. Thus, by modulating actomyosin organization, YAP may influence many actomyosin-dependent cellular characteristics, including adhesion, membrane protrusion, spreading, morphology, and cortical tension and elasticity, which in turn determine cell differentiation and tissue morphogenesis.

AB - The Hippo pathway effector Yes-associated protein (YAP) regulates liver size by promoting cell proliferation and inhibiting apoptosis. However, recent in vivo studies suggest that YAP has important cellular functions other than controlling proliferation and apoptosis. Transgenic YAP expression in mouse hepatocytes results in severe jaundice. A possible explanation for the jaundice could be defects in adherens junctions that prevent bile from leaking into the blood stream. Indeed, immunostaining of E-cadherin and electron microscopic examination of bile canaliculi of Yap transgenic livers revealed abnormal adherens junction structures. Using primary hepatocytes from Yap transgenic livers and Yap knockout livers, we found that YAP antagonizes E-cadherin-mediated cell-cell junction assembly by regulating the cellular actin architecture, including its mechanical properties (elasticity and cortical tension). Mechanistically, we found that YAP promoted contractile actin structure formation by upregulating nonmuscle myosin light chain expression and cellular ATP generation. Thus, by modulating actomyosin organization, YAP may influence many actomyosin-dependent cellular characteristics, including adhesion, membrane protrusion, spreading, morphology, and cortical tension and elasticity, which in turn determine cell differentiation and tissue morphogenesis.

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