Neurofibromatosis 2(NF2) is a dominantly inherited disorder characterized by the occurrence of multiple nervous system tumors, particularly schwannomas and meningiomas. The NF2 gene was isolated by positional cloning. The NF2 gene product has been named merlin, because of its striking similarity to ezrin, radixin and moesin (ERM), members of the protein 4.1 family thought to link cytoskeletal components with proteins in the cell membrane. Merlin thus represents a new class of tumor suppressor whose function may be mediated by interactions with the cytoskeletal network. In order to understand the function of this protein we have generated a variety of antibodies that detect merlin at ~66 kD. We have localized endogenous merlin to motile regions of cells such as leading or ruffling edges where it co-localizes with F-actin. We have observed that merlin behaves like its related members, the ERM proteins in many respects. We have identified NHE-RF, a regulatory factor for the Na+-H+ exchange as a binding partner for merlin and the ERM proteins. Recent studies on the ERM proteins have implicated a role for these proteins in actin cytoskeletal remodeling, and the Rho family of GTPase mediated cellular signaling to the actin cytoskeleton. We focus in my group to understand the putative role of merlin in actin filament assembly, in cell signaling cascades to the actin cytoskeletal network mediated primarily by the Rho family of GTpases. Our studies should provide the new knowledge on the normal function of merlin and explain the consequences of the lack of merlin in human tumor cells.

References:

• Current Opinion in Genetics and Development 6:87-92, 1996.
• Oncogene 13, 1239-47, 1996
• J. Biol. Chem. 273, 1273-1276, 1998

Mia MacColin, M.D.
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