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 journalArticlepeer-review

245 Scopus citations

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)
Number of pages1
JournalCell
Volume154
Issue number6
DOIs
StatePublished - Sep 12 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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