Disease relevance of Merlin

• The NF2 protein, called schwannomin or merlin, is absent in virtually all schwannomas, and many meningiomas and ependymomas [1].
• The involvement of calpain-dependent proteolysis of the tumor suppressor NF2 (merlin) in schwannomas and meningiomas [2].
• DNA diagnosis of neurofibromatosis 2. Altered coding sequence of the merlin tumor suppressor in an extended pedigree [3].
• The neurofibromatosis-2 homologue, Merlin, and the tumor suppressor expanded function together in Drosophila to regulate cell proliferation and differentiation [4].
• Loss of Merlin function in Drosophila results in hyperplasia of the affected tissue without significant disruptions in differentiation [4].

High impact information on Merlin

• The tumor suppressors Merlin, expanded, hippo, salvador and mob as tumor suppressor also share multiple Fat pathway phenotypes but regulate Warts activity independently [5].
• We also discuss membrane proteins to which ERM and merlin bind, including those making an indirect linkage through the PDZ-containing adaptor molecules EBP50 and E3KARP [6].
• Merlin, the product of the NF2 tumor suppressor gene, has sequence similarity to ERM proteins and binds to some of the same membrane proteins, but lacks a C-terminal F-actin binding site [6].
• Increased proteolysis of merlin by calpain in some schwannomas and meningiomas exemplifies tumorigenesis linked to the calpain-mediated proteolytic pathway [2].
• Integrin-, cadherin-, Merlin- and planar cell polarity (PCP)-dependent signaling cascades quantitatively and qualitatively program cell division during development [7].

Chemical compound and disease context of Merlin

• The enhanced proliferation of merlin-deficient NF2 schwannoma cells could be reduced in the presence of quinidine, a K(+) channel blocker, whereas the proliferation of normal Schwann cells is not affected [8].

Biological context of Merlin

• Recent studies have revealed that ERM proteins transduce growth signals, and have shed new light on how merlin links cell growth to the cytoskeleton [9].
• The neurofibromatosis-2 (NF2) gene encodes merlin, an ezrin-radixin-moesin-(ERM)-related protein that functions as a tumor suppressor [10].
• However, the cellular mechanism whereby merlin controls cell proliferation from this location is not known [11].
• We found that merlin mediates contact inhibition of growth through signals from the extracellular matrix [10].
• Recent studies suggest that Merlin may coordinate the processes of growth-factor receptor signaling and cell adhesion [12].

Anatomical context of Merlin

• Merlin colocalizes and interacts with adherens junction (AJ) components in confluent wild-type cells, suggesting that the lack of AJs and contact-dependent growth arrest in Nf2(-/-) cells directly results from the absence of merlin at sites of cell:cell contact [11].
• In order to analyze the function of merlin during embryogenesis and to develop a system to study merlin function in detail, we have disrupted the mouse Nf2 gene by homologous recombination in embryonic stem cells [13].
• Mosaic studies demonstrate that merlin function is not required cell autonomously in mesoderm, and support the proposition that merlin function is essential for the development of extraembryonic structures during early mouse development [13].
• This inhibitory function of merlin is mediated through its binding to the Pak1 PBD and by inhibiting Pak1 recruitment to focal adhesions [14].
• In 1993, a location cloning approach revealed this tumor suppressor, dubbed merlin, as a novel member of a family of proteins that link elements of the cytoskeleton and the cell membrane [15].

Associations of Merlin with other chemical compounds

• In the case of Ras, merlin acts downstream of the receptor tyrosine kinase-growth factor receptor binding protein 2 (Grb2)-SOS complex [16].
• We report that the phosphorylation of merlin at serine 518 is induced by the p21-activated kinase PAK2 [17].
• The interaction between TRBP and merlin was confirmed by glutathione S-transferase pull-down assays, co-immunoprecipitation, and co-localization experiments [18].
• The herbicides were atrazine (ATR; 2-chloro-4-ethylamino-6-isopropylamino-1,3,5-triazine) and isoxaflutole [IXF; 5-cyclopropyl-4-(2-methylsulfonyl-4-trifluormethyl-benzoyl)isoxazole], which has the commercial name Balance (Aventis Crop Science, Strasbourg, France) [19].
• A kinetic study of the chemical degradation of isoxaflutole (5-cyclopropyl-1,2-oxazol-4-yl alpha alpha alpha-trifluoro-2-mesyl-p-tolyl ketone) into its diketonitrile derivative (DKN), which is its active herbicide principle, in organic buffers at different pH values was carried out using a HPLC/UV detection method [20].

Gene context of Merlin

• Distinct cellular and subcellular patterns of expression imply distinct functions for the Drosophila homologues of moesin and the neurofibromatosis 2 tumor suppressor, merlin [21].
• Merlin interacts with HRS in the unfolded, or open, conformation [22].
• Nucleocytoplasmic transfer of the NF2 tumor suppressor protein merlin is regulated by exon 2 and a CRM1-dependent nuclear export signal in exon 15 [23].
• The NF2 protein, called schwannomin or merlin, is inactivated in virtually all schwannomas and meningiomas [24].
• Collectively, these data indicate that erbin regulates MAP kinase activation in Schwann cells and suggest that erbin links merlin to both adherens junction protein complexes and the MAP kinase signaling pathway [25].

Analytical, diagnostic and therapeutic context of Merlin

• In situ hybridization and RT-PCR analyses demonstrated that rat merlin is widely expressed during embryogenesis and early postnatal life in most tissues but becomes restricted to the brainstem, cerebellum, dorsal root ganglia, spinal cord, adrenal gland and testis in adult animals [26].
• Partial sequence analysis of the rat merlin gene demonstrated striking amino acid identity to the published mouse and human merlin gene sequences [26].
• Western blotting and immunohistochemistry with antibodies directed against the amino and carboxy termini of merlin demonstrated loss of merlin expression in all studied schwannomas, including 12 tumors lacking genetic evidence of biallelic NF2 gene inactivation [27].
• The carboxyl-terminal region of NHE-RF, downstream of the PDZ domains, interacts with the amino-terminal protein 4.1 domain-containing segment of merlin in yeast two-hybrid assays [28].
• Quantitative immunoblotting revealed that the molar ratio of merlin/ERM in cultured epithelial or non-epithelial cells was approximately 0.14 or approximately 0.05, respectively [29].

References