Data on the regulation of moesin and merlin by the urokinase receptor (uPAR): Model explaining distal activation of integrins by uPAR.

The data presented herein are connected to our research article (doi: 10.1016/j.biocel.2017.04.012) [1], in which we investigated the functional connections between the urokinase receptor (uPAR), and the ezrin/radixin/moesin (ERM) proteins, moesin and merlin [1]. Firstly, a model of action is proposed that enlightens how uPAR regulates distal integrins. In addition, data show the effects of expressing wild-type moesin or permanently active T558D mutant of moesin on angiogenesis and morphology of human aortic endothelial cells (HAEC). Additional data compare the effects of urokinase (uPA, the main ligand of uPAR) on the same cells. Lastly, we provide technical data demonstrating the effects of specific siRNA for moesin and merlin on moesin and merlin expression, respectively.

Moesin and merlin regulate urokinase receptor-dependent endothelial cell migration, adhesion and angiogenesis.

The glycosyl-phosphatidyl-inositol (GPI)-anchored urokinase receptor (uPAR) has no intracellular domain, but nevertheless initiates signalling through proximal interactions with other membrane receptors including integrins. The relationships between uPAR and ezrin/radixin/moesin (ERM) proteins, moesin and merlin have never been explored. Moesin and merlin are versatile membrane-actin links and regulators of receptors signalling, respectively. We show that uPAR controls moesin and merlin, which propagate uPAR-initiated signals and modulate integrin functions, thereby regulating uPAR activity. uPAR rapidly de-phosphorylates moesin and phosphorylates merlin inactivating both proteins, and enhancing cell migration and angiogenesis. Moesin behaves as a molecular switch turning either on or off uPAR signalling through cycles of de-activation/activation, or sustained activation, respectively. Furthermore, moesin is at the crossroads of uPAR-initiated outside-in and inside-out signalling promoting integrin-dependent cell adhesion suggesting that uPAR also activates integrins distally through moesin. Knocking down merlin expression enhanced cell migration and adhesion through different regulation of fibronectin- and vitronectin-binding integrins.

Microparticles: A Pivotal Nexus in Vascular Homeostasis and Disease.

Microvesicles (MVs) are submicron intact particles released from the cellular membrane of eukaryotic cells. MVs can be sub-categorised into microparticles (MPs), which are between 100nm- 1micron in size, and exosomes, measuring less than 100nm. Once thought to be cellular debris, MPs are now known to play important biological effector functions. Their biogenesis and release are as a result highly regulated processes in response to cellular activation or stress, and apoptosis. MPs are now known to play a crucial role in maintaining physiological homeostasis and have been demonstrated to be involved in numerous biological processes, including inflammation, cardiovascular disease, immune response, cancer dissemination, coagulation and angiogenesis. Consequently, there is active interest in studying MPs, and their 'cause and effect' in the initiation and potentiation of various pathologies. Circulating levels, both quantitative and qualitative, of MPs is thought to be a reflective index of cardiovascular competence. Therefore, studies to understand the biological relevance of the various permutations and combinations of circulating MPs, their cellular origin and bioactive cargo may lead to increased understanding of the sequelae of CVD and associated diseases. This review synopsizes our current understanding of the role of MPs in cardiovascular disease, their biogenesis and effector function, and their future use as both diagnostic and prognostic indices of cardiovascular disease.