Developmental Cell
Volume 1, Issue 1, July 2001, Pages 63-72
Journal home page for Developmental Cell

Article
The Nf2 Tumor Suppressor, Merlin, Functions in Rac-Dependent Signaling

https://doi.org/10.1016/S1534-5807(01)00009-0Get rights and content
Under an Elsevier user license
open archive

Abstract

Mutations in the neurofibromatosis type II (NF2) tumor suppressor predispose humans and mice to tumor development. The study of Nf2+/− mice has demonstrated an additional effect of Nf2 loss on tumor metastasis. The NF2-encoded protein, merlin, belongs to the ERM (ezrin, radixin, and moesin) family of cytoskeleton:membrane linkers. However, the molecular basis for the tumor- and metastasis- suppressing activity of merlin is unknown. We have now placed merlin in a signaling pathway downstream of the small GTPase Rac. Expression of activated Rac induces phosphorylation and decreased association of merlin with the cytoskeleton. Furthermore, merlin overexpression inhibits Rac-induced signaling in a phosphorylation-dependent manner. Finally, Nf2−/− cells exhibit characteristics of cells expressing activated alleles of Rac. These studies provide insight into the normal cellular function of merlin and how Nf2 mutation contributes to tumor initiation and progression.

Cited by (0)

6

Present address: Division of Signal Transduction, Beth Israel Deaconess Medical Center, and Department of Cell Biology, Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02115

7

These authors contributed equally to this work.