Direct involvement of ezrin/radixin/moesin (ERM)-binding membrane proteinsin the organization of microvilli in collaboration with activated ERM proteins
S. Yonemura et al., Direct involvement of ezrin/radixin/moesin (ERM)-binding membrane proteinsin the organization of microvilli in collaboration with activated ERM proteins, J CELL BIOL, 145(7), 1999, pp. 1497-1509
Ezrin/radixin/moesin (ERM) proteins have been thought to play a central rol
e in the organization of cortical actin-based cytoskeletons including micro
villar formation through cross-linking actin filaments and integral membran
e proteins such as CD43, CD44, and ICAM-2. To examine the functions of thes
e ERM-binding membrane proteins (ERMBMPs) in cortical morphogenesis, we ove
rexpressed ERMBMPs (the extracellular domain of E-cadherin fused with the t
ransmembrane/cytoplasmic domain of CD43, CD44, or ICAM-2) in various cultur
ed cells. In cultured fibroblasts such as L and CV-1 cells, their overexpre
ssion significantly induced microvillar elongation, recruiting ERM proteins
and actin filaments. When the ERM-binding domains were truncated from thes
e molecules, their ability to induce microvillar elongation became undetect
able. In contrast, in cultured epithelial cells such as MTD-1A and A431 cel
ls, the overexpression of ERMBMPs did not elongate microvilli. However, in
the presence of EGF overexpression of ERMBMPs induced remarkable microvilla
r elongation in A431 cells. These results indicated that ERMBMPs function a
s organizing centers for cortical morphogenesis by organizing microvilli in
collaboration with activated ERM proteins. Furthermore, immunodetection wi
th a phosphorylated ERM-specific antibody and site-directed mutagenesis sug
gested that ERM proteins phosphorylated at their COOH-terminal threonine re
sidue represent activated ERM proteins.