Merlin differentially associates with the microtubule and actin cytoskeleton.
The neurofibromatosis 2 (NF2) suppressor gene encodes a protein termed merlin (or schwannomin) with sequence similarity to a family of proteins that link the actin cytoskeleton to cell surface glycoproteins. Members of this ERM family of proteins include ezrin, radixin, and moesin. These proteins contain a carboxyl (C-) terminus actin binding site. In contrast to the ERM proteins, merlin lacks the conventional C-terminal actin binding site, but still localizes to the ruffling edge of plasma membranes. In this study, we investigate the ability of merlin to interact with actin through a nonconventional actin binding domain. We demonstrate for the first time that merlin can associate with polymerized actin in vitro by virtue of an amino (N-) terminal actin binding domain including residues 178-367. Merlin actin binding is not affected by several naturally-occurring NF2 patient mutations or alternatively spliced isoforms. These results suggest that merlin, like other ERM proteins, can directly interact with the actin cytoskeleton. In addition, merlin associates with polymerized microtubules in vitro using a novel microtubule binding region in the N-terminal region of merlin that is masked in the full-length merlin molecule, such that wild-type functional merlin in the "closed" conformation fails to bind polymerized microtubules. These microtubule association results confirm the notion that merlin exists in "open" and "closed" conformations relevant to its function as a negative growth regulator.
Xu
H M
HM
Department of Neurology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Gutmann
D H
DH
D000199:Actins / Q000378:metabolism*; D001665:Binding Sites; D001704:Biopolymers; D003599:Cytoskeleton / Q000378:metabolism*; D016515:Genes, Neurofibromatosis 2; D008565:Membrane Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D025581:Neurofibromin 2; D011487:Protein Conformation
D000199:Actins; D001704:Biopolymers; D008565:Membrane Proteins; D025581:Neurofibromin 2