Moesin is involved in microglial activation accompanying morphological changes and reorganization of the actin cytoskele
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The Journal of Physiological Sciences Open Access
ORIGINAL PAPER
Moesin is involved in microglial activation accompanying morphological changes and reorganization of the actin cytoskeleton Tomonori Okazaki1, Daichi Saito1, Masatoshi Inden2, Kotoku Kawaguchi1, Sayuri Wakimoto1, Takashi Nakahari3 and Shinji Asano1*
Abstract Moesin is a member of the ezrin, radixin and moesin (ERM) proteins that are involved in the formation and/or maintenance of cortical actin organization through their cross-linking activity between actin filaments and proteins located on the plasma membranes as well as through regulation of small GTPase activities. Microglia, immune cells in the central nervous system, show dynamic reorganization of the actin cytoskeleton in their process elongation and retraction as well as phagocytosis and migration. In microglia, moesin is the predominant ERM protein. Here, we show that microglial activation after systemic lipopolysaccharide application is partly inhibited in moesin knockout (Msn-KO) mice. We prepared primary microglia from wild-type and Msn-KO mice, and studied them to compare their phenotypes accompanying morphological changes and reorganization of the actin cytoskeleton induced by UDPstimulated phagocytosis and ADP-stimulated migration. The Msn-KO microglia showed higher phagocytotic activity in the absence of UDP, which was not further increased by the treatment with UDP. They also exhibited decreased ADP-stimulated migration activities compared with the wild-type microglia. However, the Msn-KO microglia retained their ability to secrete tumor necrosis factor α and nitric oxide in response to lipopolysaccharide. Keywords: Microglia, Moesin, Actin cytoskeleton, Phagocytosis Introduction Microglia are immune cells resident in the central nervous system. Under normal or resting conditions, microglia with numerous long and branched processes continuously survey their environment to identify abnormalities in surrounding cells. In responding to injury, they retract their processes, induce hypertrophy of their cell bodies, and rapidly migrate toward the site of injury [1]. They secrete a number of proinflammatory cytokines, including tumor necrosis factor α (TNF-α), interleukin-1β, and cytotoxic molecules such as nitric *Correspondence: [email protected] 1 Department of Molecular Physiology, College of Pharmaceutical Sciences, Ritsumeikan University, 1‑1‑1 Noji‑Higashi, Kusatsu 525‑8577, Japan Full list of author information is available at the end of the article
oxide (NO) and reactive oxygen species, [1] but also neuroprotective molecules such as interleukin-10 and TGF-β [2]. They are also engaged in the clearance of dead and dying neurons and neuronal debris by phagocytosis, which is crucial to the maintenance of brain functions [2]. Such process elongation and retraction and phagocytosis are driven by dynamic reorganization of the actin cytoskeleton [3]. Microglia contain several metabotropic P2Y (P2Y6, P2Y12, and P 2Y13) and ionotropic P2X (P2X4 and P2X7) receptors, some of
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