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The actin-binding ERM protein Moesin binds to and stabilizes microtubules at the cell cortex.

ABSTRACT: Ezrin, Radixin, and Moesin (ERM) proteins play important roles in many cellular processes including cell division. Recent studies have highlighted the implications of their metastatic potential in cancers. ERM's role in these processes is largely attributed to their ability to link actin filaments to the plasma membrane. In this paper, we show that the ERM protein Moesin directly binds to microtubules in vitro and stabilizes microtubules at the cell cortex in vivo. We identified two evolutionarily conserved residues in the FERM (4.1 protein and ERM) domains of ERMs that mediated the association with microtubules. This ERM-microtubule interaction was required for regulating spindle organization in metaphase and cell shape transformation after anaphase onset but was dispensable for bridging actin filaments to the metaphase cortex. These findings provide a molecular framework for understanding the complex functional interplay between the microtubule and actin cytoskeletons mediated by ERM proteins in mitosis and have broad implications in both physiological and pathological processes that require ERMs.

SUBMITTER: Solinet S

PROVIDER: S-EPMC3718980 | biostudies-literature |

REPOSITORIES: biostudies-literature

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THE ACTIN-BINDING MOESIN PROTEIN IS REQUIRED FOR HEAT SHOCK GENE EXPRESSION IN DROSOPHILA

Project description:The cytoskeletal actin-binding ERM (ezrin, radixin and moesin) proteins play essential role in modulating numerous signal transduction events in the cytoplasm by crosslinking actin filaments with plasma membrane proteins. The nuclear localization of ERMs has been also reported and the involvement of the single Drosophila ERM protein in nuclear mRNA export was recently described. However, because the cytoskeletal activity of ERMs is essential in the cell, and the exact mechanism of their nuclear transport is still unknown, the biological significance of the presence of ERM proteins in the nucleus has not been yet determined. Here we present the first attempt to reveal the in vivo relevance of the nuclear localization of the cytoskeletal ERM protein, Drosophila Moesin. With the help of a nuclear export signal (NES) we decreased the amount of Moesin in the nuclei of the animal. As a result, we observed various developmental defects, demonstrating for the first time the importance of ERM function in the cell nucleus. Transcriptome analysis of the mutant flies revealed, that the lack of nuclear Moe function leads to expression change of about 700 genes, among them a group of heat shock genes. This result together with additional findings demonstrates that in Drosophila, the expression of protein chaperons requires the nuclear functions of Moesin.

2020-08-06 | GSE155778 | GEO

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Project description:We investigated how the neural cell adhesion molecule L1 mediates neurite outgrowth through L1-L1 homophilic interactions. Wild-type L1 and L1 with mutations in the cytoplasmic domain (CD) were introduced into L1 knock-out neurons, and transfected neurons were grown on an L1 substrate. Neurite length and branching were compared between wild-type L1 and L1CD mutations. Surprisingly, the L1CD is not required for L1-mediated neurite outgrowth but plays a critical role in neurite branching, through both the juxtamembrane region and the RSLE region. We demonstrate that both regions serve as ezrin-moesin-radixin-binding sites. A truncation mutant that deletes 110 of 114 amino acids of the L1CD still supports neurite outgrowth on an L1 substrate, suggesting that a coreceptor binds to L1 in cis and mediates neurite outgrowth and that L1-ankyrin interactions are not essential for neurite initiation or outgrowth. These data are consistent with a model in which L1 can influence L1-mediated neurite outgrowth and branching through both the L1CD and a coreceptor.

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Structural basis for the phosphorylation-regulated interaction between the cytoplasmic tail of cell polarity protein crumbs and the actin-binding protein moesin.

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