H2020Индивидуална стипендия2016–2017

membrane-ezrin-actin · Membrane-ezrin-actin interactions mediated by ezrin binding proteins in reconstituted systems

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2016-01-01 → 2017-12-31
Финансиране от ЕС: 173 076 €
Участници: 1
Схема: MSCA-IF-EF-ST

Линиите свързват координатора с партньорите.

Накратко на български

Протеинът езрин свързва клетъчните мембрани с цитоскелета, като се разполага както върху изпъкнали, така и върху вдлъбнати повърхности. Разбирането на този механизъм помага да се разбере как се контролира формата на клетката и защо се появяват дефекти при рак и ембрионалното развитие.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Membrane-ezrin-actin interactions mediated by ezrin binding proteins in reconstituted systems

Ezrin, a member of the ezrin-radixin-moesin (ERM) protein family, plays a crucial role in linking the cellular membranes to the actin cytoskeleton. Ezrin participates in cell shape control that is involved in diverse cellular functions including cell adhesion and migration. It has been shown that ezrin malfunctioning has severe consequences in cancer progression and in embryonic development such as abnormal villus morphogenesis. Thus, it is important to understand how cells precisely regulate the membrane localization and function of ezrin. In cells ezrin is enriched in actin-rich plasma membrane structures such as filopodia and microvilli. In these membrane protrusions ezrin is located at the cytosolic side wherein the membrane has a negative mean curvature. This suggests that ezrin has a strong affinity for negatively curved membranes; in other words, ezrin may be a negative membrane curvature-sensing protein. However, ezrin is also associated with some intracellular vesicles including endosomes, wherein the membranes have a positive mean membrane curvature. Moreover, ezrin is also found at flat regions of the plasma membrane, such as at the cortex-membrane interface and at the surface of membrane blebs. How the same protein can be a positive and a negative membrane curvature sensor is a conundrum that had to be solved. In this project, we aimed to decipher bio-physical mechanisms underlying the enrichment of ezrin on curved membranes. By using cell biology and in vitro approaches combining lipid vesicles and purified ezrin, we showed that ezrin association with curved membranes requires a specific conformation of the protein or interaction with a curvature-sensitive partner.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

Microvilli are tube-like membrane protrusions containing bundles of actin filaments located at the apical surface of epithelial cells. A key component of these microvilli is ezrin, a member of the Ezrin/Radixin/Moesin protein family, which provides a regulated linkage between the plasma membrane and the actin cytoskeleton. The critical role of ezrin in microvillar morphogenesis has been demonstrated. However, how ezrin is recruited to the apical surface of the cells and how ezrin contributes to the stability of microvillar morphogenesis remain elusive. Recently, a few ezrin binding partners, such as EBP50 and Eps8, have been identified and shown to function synergistically with ezrin in membrane and actin remodelling in cells. The precise mechanisms and implications of their interactions in microvillar morphogenesis are not well understood. Lately, I-BAR domain protein IRSp53 was found to colocalize with ezrin in microvilli and interact with both EBP50 and Eps8, as ezrin does. Given that I-BAR domain proteins participate in the formation of many cellular protrusions, such as filopodia, ezrin and I-BAR domain proteins may work synergistically in membrane remodelling. The goal of this proposal is to better understand the interaction of ezrin, the membrane and actin, and the role of ezrin binding proteins and I-BAR domain proteins in this interaction by using reconstituted model systems based on purified proteins combined with supported lipid bilayers or giant unilamellar vesicles. In parallel, potential common binding partners of ezrin and I-BAR domain proteins will be identified, and their role in mediating the interaction of ezrin and I-BAR domain proteins on membranes will be studied. This project will thus lead to an improved understanding of the membrane and actin remodelling activity of ezrin, and advance our knowledge of cell and eventually tissue morphogenesis.

Оригинален текст от CORDIS (на английски).

Участници

INSTITUT CURIE · ParisКоординаторФранция