MERLIN DIFFERS FROM MOESIN IN BINDING TO F-ACTIN AND IN ITS INTRAMOLECULAR AND INTERMOLECULAR INTERACTIONS

The neurofibromatosis type 2 (NF2) tumor suppressor gene encodes merli n, a protein with homology to the cell membrane/F-actin linking protei ns, moesin, ezrin and radixin. Unlike these closely related proteins, merlin lacks a C-terminal F-actin binding site detectable by actin blo t overlays, and the GFP-tagged merlin C-terminal domain co-distributes with neither stress fibers nor cortical actin in NIH3T3 cells. Merlin also differs from the other three proteins in its inter- and intramol ecular domain interactions, as shown by in vitro binding and yeast two -hybrid assays. As is true for ezrin, moesin and radixin, the N- and C -terminal domains of merlin type 1 bind to each other. However, full-l ength merlin and its N- and C-terminal domains, as well as the C-termi nal domain of ezrin, interact with other full-length merlin type 1 mol ecules, and its C-terminal domain interacts with itself. Merlin 1 func tion in cells may thus depend on intra- and intermolecular interaction s and their modulation, which include interactions with other members of this protein family. (C) 1998 Academic Press.