ERM-proteins

ERM is the acronym for "Ezrin/Radixin/Moesin". ERM stands for a protein family consisting of the three highly conserved proteins: ezrin, radixin and moesin (ERM) (Sato et al. 1992). EMR proteins link integral membrane proteins to the actin cytoskeleton and relay signals into the cell interior. ERM proteins regulate plasma membrane plasticity and are responsible for the formation of specific membrane structures. In this way, they mediate the formation of microvilli, cell contacts, membrane protrusions and division furrows (Bretscher et al. 2000).

Ezrin/Radixin/Moesin as members of the band 4.1 protein family. ERM proteins have arisen by gene duplication and show strong homologies to each other. The DNA sequence of murine ezrin is 75% identical to that of radixin, and 72% identical to that of moesin. The DNA sequences of radixin and moesin (MSN) are 80% identical (Tsukita et al. 1997). This indicates that ERM proteins have similar, and in some cases redundant, functions.

ERM proteins are expressed in an organ- and cell-type-specific manner. Ezrin is found primarily in intestine, stomach, lung, and kidney, whereas moesin is found primarily in lung and spleen, and radixin is found in liver and intestine (Louvet-Vallee, 2000). Ezrin is primarily expressed in epithelial cells, moesin in endothelial cells, hematopoietic cells but also normal skin and in epithelial tumors(expressed (Ichikawa T et al. 1998).

In human lymphocytes, monocytes and neutrophils, ezrin and moesin are expressed, but not radixin. In platelets, moesin is predominantly detected (Fehlner K 2013). Mice in which one of the three ERM proteins has been deactivated by targeted gene modification often show abnormalities only in the tissues and cell populations in which the corresponding ERM protein is expressed alone.

ERM proteins not only show high sequence homologies among themselves, but are also 48% identical to another protein, Merlin ("Moesin-Ezrin-Radixin-like Protein"). Merlin is a tumor suppressor.

In humans, a defect of the merlin-encoding gene NF2 leads to dominantly inherited neurofibromatosis 2, resulting in the formation of schwannomas (= benign tumors of the central nervous system) and mesotheliomas (Martuza & Eldridge, 1988; Bianchi et al., 1995). Together, ERM proteins and Merlin belong to the Band 4.1 protein superfamily. This family takes its name from an erythrocyte membrane protein called Band 4.1 protein. This connects the plasma membrane to the cytoskeleton and regulates the deformation and stability of erythrocytes.

ERM proteins bind to the cytoplasmic region of CD44 (Tsukita et al., 1994), a receptor for extracellular matrix components (hyaluronic acid, collagen, laminin, and fibronectin). Furthermore, ERM proteins bind to the cytoplasmic domain of CD43 and are thereby recruited to the uropod of lymphocytes (Serrador et al. 1998).

Moesin interacts with ICAM-3 (Serrador et al. 1997) and ezrin interacts with ICAM-1 and ICAM-2 (Helander et al., 1996; Heiska et al., 1998). In addition, ezrin and moesin associate with the cytoplasmic region of L-selectin. In addition, ERM proteins bind indirectly via adaptor proteins to the cytoplasmic domain of "multipass" transmembrane proteins and are involved in their signal transduction (Bretscher et al. 2000; Louvet-Vallee 2000; Bretscher et al. 2002).

1. Bretscher A et al (2000) ERM-Merlin and EBP50 protein families in plasma membrane organization and function. Annu Rev Cell Dev Biol 16: 113-143.
2. Bretscher A et al (2002) ERM proteins and merlin: integrators at the cell cortex. Nat Rev Mol Cell Biol 3: 586-99.
3. Fehlner K (2013) Activity regulation of ERM (ezrin/radixin/moesin) proteins and their importance for LFA-1 mediated T cell migration . Inagural dissertation at the TechnischeUniversität München. Chair of Chemistry of Biopolymers.
4. Louvet-Vallee S (2000). ERM proteins: from cellular architecture to cell signaling. Biol Cell 92, 305-316
5. Martuza RL et al (1988) Neurofibromatosis 2 (bilateral acoustic neurofibromatosis). N Engl J Med 318: 684-688.
6. Sato N et al. (1992) A gene family consisting of ezrin, radixin and moesin. Its specific localization at actin filament/plasma membrane association sites. J Cell Sci 103: 131-143.
7. Serrador JM et al. (1997) Moesin interacts with the cytoplasmic region of intercellular adhesion molecule-3 and is redistributed to the uropod of T lymphocytes during cellpolarization. J Cell Biol 138, 1409-1423.
8. Tsukita S et al (1994) ERM family members as molecular linkers between the cell surface glycoprotein CD44 and actin-based cytoskeletons. J Cell Biol 126: 391-401.
9. Tsukita S et al (1997) ERM proteins: head-to-tail regulation of actinplasma membrane interaction. Trends Biochem Sci 22: 53-58.