Moesin-ezrin-radixin-like protein merlin: Its conserved and distinct functions from those of ERM proteins

Neurofibromatosis type 2 ( NF2 ), which encodes merlin (moesin-ezrin-radixin-like protein), belongs to the band 4.1, ezrin, radixin, moesin (FERM) domain-containing 4.1 superfamily. Merlin shares sequence homology with ERM proteins, is evolutionarily conserved, and acts as a tumour suppressor. Here, we describe the molecular functions of merlin from a biophysical point of view. We describe the structural basis for the merlin regulatory mechanisms based on its interaction with phosphatidylinositol 4,5-bisphosphate (PI(4,5)P 2 ) along with its interaction partners, and then describe its physiological functions in cell-cell adhesions. Elucidation of these merlin functions will lead to a clear understanding of its fundamental roles in cells and tissues. • Merlin plays a role in cell–cell adhesions and contact inhibition of proliferation. • Merlin changes its conformation upon PI(4,5)P 2 -binding. • Membrane-binding affinity can be determined by liposome cosedimentation/coflotation assays. • FRAP is applicable to quantify merlin dynamics on the membranes. • Merlin induces liquid-liquid phase separation.