title: Interaction between two isoforms of the NF2 tumor suppressor protein, merlin, and between merlin and ezrin, suggests modulation of ERM proteins by merlin.
abstract: The product of the neurofibromatosis type II (NF2) tumor suppressor gene, merlin, is closely related to the ezrin-radixin-moesin (ERM) family, a group of proteins believed to link the cytoskeleton to the plasma membrane. Mutation in the NF2 locus is associated with Schwann cell tumors (schwannomas). The two predominant merlin isoforms, I and II, differ only in the carboxy-terminal 16 residues and only isoform I is anti-proliferative. Merlin lacks an actin-binding domain conserved among ezrin, radixin and moesin. Because merlin, ezrin and moesin are co-expressed in Schwann cells, and all homodimerize, we have examined whether merlin and ezrin dimerize with one another. We found by immunoprecipitation and yeast two-hybrid assays that both merlin isoforms interact with ezrin. The interaction occurs in a head-to-tail orientation, with the amino-terminal half of one protein interacting with the carboxy-terminal half of the other. The two merlin isoforms behave differently in their interaction with ezrin. Isoform I binds only ezrin whose carboxy-terminus is exposed, whereas isoform II binds ezrin regardless of whether ezrin is in the open or closed conformation. The heterodimerization of merlin is a much stronger interaction than the interaction between either merlin isoform and ezrin, and can inhibit merlin-ezrin binding. This suggests that, in vivo, merlin dimerization could regulate merlin-ERM protein interaction, and could thus indirectly regulate other interactions involving ERM proteins.
authors.affiliation: Department of Cell Biology, Neurobiology & Anatomy, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0521, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Meng
authors.forename: D J
authors.initials: DJ
authors.lastname: Lowrie
authors.forename: H
authors.initials: H
authors.lastname: Sun
authors.forename: E
authors.initials: E
authors.lastname: Dorsey
authors.forename: P D
authors.initials: PD
authors.lastname: Pelton
authors.forename: A M
authors.initials: AM
authors.lastname: Bashour
authors.forename: J
authors.initials: J
authors.lastname: Groden
authors.forename: N
authors.initials: N
authors.lastname: Ratner
authors.forename: W
authors.initials: W
authors.lastname: Ip
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001798:Blood Proteins / Q000235:genetics / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D016518:Neurofibromatosis 2 / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D025581:Neurofibromin 2; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics* / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D012583:Schwann Cells / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured; D000099149:Ezrin
chemical_list: D001798:Blood Proteins; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D025581:Neurofibromin 2; D010750:Phosphoproteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D000099149:Ezrin; C071058:moesin; C071776:radixin