The ERM protein family, which consists of three closely related proteins in vertebrates,
ezrin, radixin, and moesin (ERM), is an ancient and important group of cytoplasmic
actin-binding and organizing proteins. With their FERM domain, ERMs bind various transmembrane
proteins and anchor them to the actin cortex through their C-terminal F-actin binding
domain, thus they are major regulators of actin dynamics in the cell. ERMs participate
in many fundamental cellular processes, such as phagocytosis, microvilli formation,
T-cell activation and tumor metastasis. We have previously shown that, besides its
cytoplasmic activities, the single ERM protein of Drosophila melanogaster, moesin,
is also present in the cell nucleus, where it participates in gene expression and
mRNA export. Here we study the mechanism by which moesin enters the nucleus. We show
that the nuclear import of moesin is an NLS-mediated, active process. The nuclear
localization sequence of the moesin protein is an evolutionarily highly conserved,
conventional bipartite motif located on the surface of the FERM domain. Our experiments
also reveal that the nuclear import of moesin does not require PIP2 binding or protein
activation, and occurs in monomeric form. We propose, that the balance between the
phosphorylated and non-phosphorylated protein pools determines the degree of nuclear
import of moesin.