XSpatial organization of hippo signaling at the plasma membrane mediated by the tumor suppressor merlin/NF2

Feng Yin, Jianzhong Yu, Yonggang Zheng, Qian Chen, Nailing Zhang, Duojia Pan

Research output: Contribution to journalArticle

204 Citations (Scopus)

Abstract

Although Merlin/NF2 was discovered two decades ago as a tumor suppressor underlying Neurofibromatosis type II, its precise molecular mechanism remains poorly understood. Recent studies in Drosophila revealed a potential link between Merlin and the Hippo pathway by placing Merlin genetically upstream of the kinase Hpo/Mst. In contrast to the commonly depicted linear model of Merlin functioning through Hpo/Mst, here we show that in both Drosophila and mammals, Merlin promotes downstream Hippo signaling without activating the intrinsic kinase activity of Hpo/Mst. Instead, Merlin directly binds and recruits the effector kinase Wts/Lats to the plasma membrane. Membrane recruitment, in turn, promotes Wts phosphorylation by the Hpo-Sav kinase complex. We further show that disruption of the actin cytoskeleton promotes Merlin-Wts interactions, which implicates Merlin in actin-mediated regulation of Hippo signaling. Our findings elucidate an important molecular function of Merlin and highlight the plasma membrane as a critical subcellular compartment for Hippo signal transduction.

Original languageEnglish (US)
JournalCell
Volume154
Issue number6
DOIs
StatePublished - Sep 12 2013

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Neurofibromin 2
Cell membranes
Tumors
Cell Membrane
Neoplasms
Phosphotransferases
Actins
Neurofibromatosis 2
Signal transduction
Phosphorylation
Mammals
Actin Cytoskeleton
Drosophila
Linear Models
Signal Transduction

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

XSpatial organization of hippo signaling at the plasma membrane mediated by the tumor suppressor merlin/NF2. / Yin, Feng; Yu, Jianzhong; Zheng, Yonggang; Chen, Qian; Zhang, Nailing; Pan, Duojia.

In: Cell, Vol. 154, No. 6, 12.09.2013.

Research output: Contribution to journalArticle

Yin, Feng ; Yu, Jianzhong ; Zheng, Yonggang ; Chen, Qian ; Zhang, Nailing ; Pan, Duojia. / XSpatial organization of hippo signaling at the plasma membrane mediated by the tumor suppressor merlin/NF2. In: Cell. 2013 ; Vol. 154, No. 6.
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