Neurofibromatosis type II (NF2), is a debilitating disease whose clinical hallmark is the development of bilateral vestibular Schwannomas. Tumor deletion studies and genetic linkage studies indicate that loss or inactivation of the NF2 gene on chromosome 22 leads to tumor formation. NF2 codes for a protein, merlin, which has high homology at the N- terminus to the ERM family of proteins. These proteins function by linking the cytoskeletal elements to the plasma membrane. Merlin may therefore function as a tumor suppressor by regulating the cellular responses to growth factor stimulation, other external stimuli or could assist in the stabilization of cell-cell or cell-substrate attachment. This study will focus on the role of merlin in Schwann cells and how loss of merlin contributes to tumor formation. Both functional and localization studies of merlin in normal Schwann cells, Schwann cells dissociated from human tumors and Schwann cells with down-regulated merlin (by transfection with antisense NF2 cDNA) will be performed. Some preliminary results already suggest that loss of merlin affects rat Schwann cells by altering neuron-Schwann cell ractions. These studies should improve our understanding of how loss of merlin contributes to tumor formation and, by identifying possible modulators, design of appropriate therapies could be envisioned.
