THE MERLIN TUMOR SUPPRESSOR LOCALIZES PREFERENTIALLY IN MEMBRANE RUFFLES

: Merlin is a tumor suppressor whose inactivation underlies the familial schwannomas and meningiomas of neurofibromatosis 2 and their sporadic counterparts. It bears striking similarity to the ERM proteins, ezrin, radixin and moesin, members of the protein 4.1 superfamily that link proteins in the cytoskeleton and the plasma membrane. We have generated polyclonal and monoclonal antibodies that detect merlin as an approximately 66 kD protein in many different cell types. Using indirect immunofluorescence we have for the first time visualized endogenous merlin and localized it to the motile regions, such as leading or ruffling edges, in human fibroblast and meningioma cells. Merlin co-localizes with F-actin in these motile regions but is not associated with stress fibers. Merlin does not localize to the same structures as either ezrin or moesin in human meningioma cells, suggesting a function distinct from these ERMs. Thus, merlin is associated with motile regions of the cell and its participation in these structures may be intimately involved in control of proliferation in Schwann cells and meningeal cells.