ArticleMolecular and cellular biology2011
FERM domain phosphoinositide binding targets merlin to the membrane and is essential for its growth-suppressive function.
Article in Molecular and cellular biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 63 citations in OpenAlex.
- Modulating PAK1: Accessory Proteins as Promising Therapeutic Targets.Biomolecules · 2025Review
- Lead exposure promotes NF2-wildtype meningioma cell proliferation through the Merlin-Hippo signaling pathway.Environmental health and preventive medicine · 2025Article
- Functional annotation of the Hippo pathway somatic mutations in human cancers.Nature communications · 2024Article
- PI4P-mediated solid-like Merlin condensates orchestrate Hippo pathway regulation.Science (New York, N.Y.) · 2024Article
- Non-vesicular phosphatidylinositol transfer plays critical roles in defining organelle lipid composition.The EMBO journal · 2024Article
- PIP5Kγ Mediates PI(4,5)P2/Merlin/LATS1 Signaling Activation and Interplays with Hsc70 in Hippo-YAP Pathway Regulation.International journal of molecular sciences · 2023Article
- HIV Infection: Shaping the Complex, Dynamic, and Interconnected Network of the Cytoskeleton.International journal of molecular sciences · 2023Review
- Missense variant interaction scanning reveals a critical role of the FERM domain for tumor suppressor protein NF2 conformation and function.Life science alliance · 2023Article
- Lipid kinase PIP5Kα contributes to Hippo pathway activation via interaction with Merlin and by mediating plasma membrane targeting of LATS1.Cell communication and signaling : CCS · 2023Article
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- Intrinsically disordered region of talin's FERM domain functions as an initial PIPBiophysical journal · 2023Article
- Article
- Conformational flexibility determines the Nf2/merlin tumor suppressor functions.Matrix biology plus · 2021Article
- RAC1 Activation as a Potential Therapeutic Option in Metastatic Cutaneous Melanoma.Biomolecules · 2021Review
- Toward Understanding the Molecular Role of SNX27/Retromer in Human Health and Disease.Frontiers in cell and developmental biology · 2021Review
- Critical roles of phosphoinositides and NF2 in Hippo pathway regulation.Genes & development · 2020Article
- Enhanced Dendritic Actin Network Formation in Extended Lamellipodia Drives Proliferation in Growth-Challenged Rac1Developmental cell · 2019Article
- Two Sides of the Coin: Ezrin/Radixin/Moesin and Merlin Control Membrane Structure and Contact Inhibition.International journal of molecular sciences · 2019Review
- Proximity biotinylation identifies a set of conformation-specific interactions between Merlin and cell junction proteins.Science signaling · 2019Article
- Regulation of the Hippo Pathway by Phosphatidic Acid-Mediated Lipid-Protein Interaction.Molecular cell · 2018Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The neurofibromatosis type 2 tumor suppressor protein, merlin, is related to the ERM (ezrin, radixin, and moesin) family of plasma membrane-actin cytoskeleton linkers. For ezrin, phosphatidylinositol 4,5-bisphosphate (PIP(2)) binding to the amino-terminal FERM domain is required for its conformational activation, proper subcellular localization, and function, but less is known about the role of phosphoinositide binding for merlin. Current evidence indicates that association with the membrane is important for merlin to function as a growth regulator; however, the mechanisms by which merlin localizes to the membrane are less clear. Here, we report that merlin binds phosphoinositides, including PIP(2), via a conserved binding motif in its FERM domain. Abolition of FERM domain-mediated phosphoinositide binding of merlin displaces merlin from the membrane and releases it into the cytosol without altering the folding of merlin. Importantly, a merlin protein whose FERM domain cannot bind phosphoinositide is defective in growth suppression. Retargeting the mutant merlin into the membrane using a dual-acylated amino-terminal decapeptide from Fyn is sufficient to restore the growth-suppressive properties to the mutant merlin. Thus, FERM domain-mediated phosphoinositide binding and membrane association are critical for the growth-regulatory function of merlin.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.