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 generat ed polyclonal and monoclonal antibodies that detect merlin as an simil ar to 66 kD protein in many different cell types, Using indirect immun ofluorescence we have for the first time visualized endogenous merlin and localized it to the motile regions, such as leading or ruffling ed ges, in human fibroblast and meningioma cells. Merlin co-localizes wit h F-actin in these motile regions but is not associated with stress fi bers. Merlin does not localize to the same structures as either ezrin or meosin in human meningioma cells, suggesting a function distinct fr om these ERMs. Thus, merlin is associated with motile regions of the c ell and its participation in these structures may be intimately involv ed in control of proliferation in Schwann cells and meningeal cells.