The NF2 tumor suppressor Merlin and the ERM proteins interact with N-WASP and regulate its actin polymerization function.
The function of the NF2 tumor suppressor merlin has remained elusive despite increasing evidence for its role in actin cytoskeleton reorganization. The closely related ERM proteins (ezrin, radixin, and moesin) act as linkers between the cell membrane and cytoskeleton, and have also been implicated as active actin reorganizers. We report here that merlin and the ERMs can interact with and regulate N-WASP, a critical regulator of actin dynamics. Merlin and moesin were found to inhibit N-WASP-mediated actin assembly in vitro, a function that appears independent of their ability to bind actin. Furthermore, exogenous expression of a constitutively active ERM inhibits N-WASP-dependent Shigella tail formation, suggesting that the ERMs may function as inhibitors of N-WASP function in vivo. This novel function of merlin and the ERMs illustrates a mechanism by which these proteins directly exert their effects on actin reorganization and also provides new insight into N-WASP regulation.
Manchanda
Nitasha
N
Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA.
Lyubimova
Anna
A
Ho
Hsin-Yi Henry
HY
James
Marianne F
MF
Gusella
James F
JF
Ramesh
Narayanaswamy
N
Snapper
Scott B
SB
Ramesh
Vijaya
V
D000199:Actins / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism; D015153:Blotting, Western; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005982:Glutathione Transferase / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008856:Microscopy, Fluorescence; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000378:metabolism; D025581:Neurofibromin 2 / Q000737:chemistry* / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012760:Shigella / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal
D000199:Actins; D000911:Antibodies, Monoclonal; D001798:Blood Proteins; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D025581:Neurofibromin 2; C495771:WASL protein, human; C495772:Wasl protein, mouse; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal; C071776:radixin; D049452:Green Fluorescent Proteins; D005982:Glutathione Transferase