Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.11.8 (FAST)
 758 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Correct spindle orientation is achieved through signaling pathways that provide a molecular link between the cell cortex and spindle microtubules in an F-actin-dependent manner. A conserved cortical protein complex, composed of LGN (also known as GPSM2), NuMA (also known as NUMA1) and dynein-dynactin, plays a key role in establishing proper spindle orientation. It has also been shown that the actin-binding protein MISP and the ERM family, which are activated by lymphocyte-oriented kinase (LOK, also known as STK10) and Ste20-like kinase (SLK) (hereafter, SLK/LOK) in mitosis, regulate spindle orientation. Here, we report that MISP functions downstream of the ERM family member ezrin and upstream of NuMA to allow optimal spindle positioning. We show that MISP directly interacts with ezrin and that SLK/LOK-activated ezrin ensures appropriate cortical MISP levels in mitosis by competing with MISP for actin-binding sites at the cell cortex. Furthermore, we found that regulation of the correct cortical MISP levels, by preventing its excessive accumulation, is essential for crescent-like polarized NuMA localization at the cortex and, as a consequence, leads to highly dynamic astral microtubules. Our results uncover how appropriate MISP levels at the cortex are required for proper NuMA polarization and, therefore, an optimal placement of the mitotic spindle within the cell.This article has an associated First Person interview with the first author of the paper.
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PMID:Activated ezrin controls MISP levels to ensure correct NuMA polarization and spindle orientation. 2966 40

Cells of transporting epithelia are characterized by the presence of abundant F-actin-based microvilli on their apical surfaces. Likewise, auditory hair cells have highly reproducible rows of apical stereocilia (giant microvilli) that convert mechanical sound into an electrical signal. Analysis of mutations in deaf patients has highlighted the critical components of tip links between stereocilia, and related structures that contribute to the organization of microvilli on epithelial cells have been found. Ezrin/radixin/moesin (ERM) proteins, which are activated by phosphorylation, provide a critical link between the plasma membrane and underlying actin cytoskeleton in surface structures. Here, we outline recent insights into how microvilli and stereocilia are built, and the roles of tip links. Furthermore, we highlight how ezrin is locally regulated by phosphorylation, and that this is necessary to maintain polarity. Localized phosphorylation is achieved through an intricate coincidence detection mechanism that requires the membrane lipid phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] and the apically localized ezrin kinase, lymphocyte-oriented kinase (LOK, also known as STK10) or Ste20-like kinase (SLK). We also discuss how ezrin-binding scaffolding proteins regulate microvilli and how, despite these significant advances, it remains to be discovered how the cell polarity program ultimately interfaces with these processes.
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PMID:Regulation of actin-based apical structures on epithelial cells. 3033 33