DISTINCT CELLULAR AND SUBCELLULAR PATTERNS OF EXPRESSION IMPLY DISTINCT FUNCTIONS FOR THE DROSOPHILA HOMOLOGS OF MOESIN AND THE NEUROFIBROMATOSIS-2 TUMOR-SUPPRESSOR, MERLIN

Interest in members of the protein 4.1 superfamily, which includes the ezrin-radixin-moesin (ERM) group, has been stimulated recently by the discovery that the human neurofibromatosis 2 (NF2) tumor suppressor g ene encodes an ERM-like protein, merlin. Although many proteins in thi s family are thought to act by linking the actin-based cytoskeleton to transmembrane proteins, the cellular functions of merlin have not bee n defined. To investigate the cellular and developmental functions of these proteins, we have identified and characterized Drosophila homolo gues of moesin and of the NF2 tumor suppressor merlin (Dmerlin). Using specific antibodies, we show that although these proteins are frequen tly coexpressed in developing tissues, they display distinct subcellul ar localizations. While Dmoesin is observed in continuous association with the plasma membrane, as is typical for an ERM family protein, Dme rlin is found in punctate structures at the membrane and in the cytopl asm. Investigation of Dmerlin in cultured cells demonstrates that it i s associated with endocytic compartments. As a result of these studies , we propose that the merlin protein has unique functions in the cell which differ from those of other ERM family members.