An essential step during clearance of apoptotic cells is the recognition of phosphatidylserine (PS) exposed on apoptotic cells by its receptors on phagocytes. Tim-4 directly binding to PS and functioning as a tethering receptor for phagocytosis of apoptotic cells has been extensively studied over the past decade. However, the molecular mechanisms by which Tim-4 collaborates with other engulfment receptors during efferocytosis remain elusive. By comparing efferocytosis induced by Tim-4 with that by Anxa5-GPI, an artificial tethering receptor, we found that Tim-4 possesses auxiliary machinery to induce a higher level of efferocytosis than Anxa5-GPI. To search for that, we performed a yeast two-hybrid screen and identified Fibronectin (Fn1) as a novel Tim-4-associating protein. Tim-4 directly associated with Fn1 and formed a complex with integrins via the association of Fn1. Through Tim-4 −/− mice and cell-based assays, we found that modulation of the Fn1 level affected efferocytosis induced by Tim-4 and disruption of the interaction between Tim-4 and Fn1 abrogated Tim-4mediated efferocytosis. In addition, Tim-4 depletion attenuated integrin signaling activation and perturbation of integrin signaling suppressed Tim-4-promoted efferocytosis. Taken together, the data suggest that Fn1 locates Tim-4 and integrins in close proximity by acting as a scaffold, resulting in synergistic cooperation of Tim-4 with integrins for efficient efferocytosis.

Elmo is an evolutionarily conserved mammalian ortholog of Caenorhabditis elegans CED-12 with proposed roles during the removal of apoptotic cells, cell migration, neurite outgrowth, and myoblast fusion (Katoh and Negishi (2003) [1], Park and Tosello (2007) [2], Grimsley et al. (2004) [3], Hamoud et al. (2014) [4]). Elmo mediates these cellular processes by interacting with various proteins located in the plasma membrane, cytoplasm and nucleus, and by modulating their activities although it has no intrinsic catalytic activity (Park and Tosello (2007) [2], Hamoud et al. (2014) [4], Li et al. (2013) [5], Margaron, Fradet and Cote (2013) [6], and Mauldin et al. (2013)[7]). Because there are a limited number of proteins known to interact with Elmo, we performed a yeast two-hybrid screen using Elmo1 as bait to identify Elmo1-interacting proteins and to evaluate their mode of regulation. Arhgef16 was one of the proteins identified through the screen and subsequent analyses revealed that Arhgef16 interacted with Elmo1 in mammalian cells as well. Expression of Arhgef16 in phagocytes promoted engulfment of apoptotic cells, and engulfment mediated by Arhgef16 increased synergistically in the presence of Elmo1 but was abrogated in the absence of Elmo1. In addition, Arhgef16-mediated removal of apoptotic cells was dependent on RhoG, but independent of Dock1. Taken together, this study suggests that the newly identified Elmo1-interacting protein, Arhgef16, functions synergistically with Elmo1 to promote clearance of apoptotic cells in a RhoG-dependent and Dock1-independent manner.

Ephexin4, a guanine nucleotide-exchange factor for RhoG, promotes engulfment of apoptotic cells and cancer cell migration in a RhoG-dependent manner, which is synergistically augmented by Elmo1, an Ephexin4-interacting protein. However, the underlying molecular mechanism remains elusive. Here, we report a mechanism by which Elmo1 cooperates with Ephexin4 to activate RhoG. We found that Ephexin4 activity was increased by elimination of its SH3 domain which intermolecularly interacts with the N20 region of Ephexin4. This interaction prevented RhoG from binding to Ephexin4 and thus inhibited RhoG activation. Moreover, we also found that Elmo1 associated with the SH3 domain as well as the N20 region and competed with the SH3 domain for binding to the N20 region, interrupting the interaction of the SH3 domain with the N20 region and thereby promoting RhoG binding to Ephexin4. In addition, the activity of Ephexin4 lacking the SH3 domain was comparable to that of Ephexin4 with Elmo1. Taken together, the data suggest that Elmo1 relieves the steric hindrance of Ephexin4 generated by the intermolecular interaction of the SH3 domain and makes Ephexin4 more accessible to RhoG.

A remarkable enhancement of the LIB electrode activity of graphene-based nanocomposites can be achieved via the incorporation of clay nanosheets.

The galvanic exchange reaction of an exfoliated 2D layered metal oxide nanosheet (NS) with excess substituent metal cations enables the synthesis of a mixed metal oxide 2D NS with controllable cation compositions and physicochemical properties. The reaction of the exfoliated MnO NS with Fe or Sn ions at 90 °C induces the uniform galvanic replacement of Mn ions with these substituent ions, whereas the same reaction at 25 °C results in the intercalative restacking of the negatively-charged MnO NS with Fe or Sn cations. Upon the galvanic exchange reaction, the highly anisotropic MnO 2D NS retains its original 2D morphology and layered structure, which is in stark contrast to 0D nanoparticles yielding hollow nanospheres via the galvanic exchange reaction. This observation is attributable to the thin thickness of the 2D NS allowing the simultaneous replacement of all the component surface-exposed metal ions. The resulting substitution of the MnO NS with Fe and Sn ions remarkably improves the electrode performance of the carbon-coated derivatives of the MnO NS for lithium ion batteries. The present study clearly demonstrates that the galvanic exchange reaction can provide an efficient method not only to tailor cation compositions but also to improve the functionalities of 2D metal oxide NSs and their carbon-coated derivatives.

Single crystalline β-Na0.33V2O5and α-V2O5nanowires were prepared with pH controlled precursors.

What is the most significant result of this study? An efficient synthetic strategy to explore high-performance Na-ion electrode materials was developed by employing exfoliated metal oxide nanosheets as an additive for graphene-based nanocompo-sites. The incorporation of small amount of metal oxide nanosheets into metal-chalcogenide-graphene nanocomposites is quite effective in improving the nanoscale mixing of components and in enhancing the porosity of composite structure. These new nanocom-posite materials show much better Na-ion electrode performance with larger discharge capacity and higher rate characteristics than the metal oxide-free nanocomposite. What prompted you to investigate this topic/problem? Recently,w ef ound that the incorporation of exfoliated metal oxide nanosheets leads to the significant improvement of the pore and composite structures of graphene-based nanocomposites. Considering that many graphene-based nanocomposites show promising Na-ion electrode functionalities, we tried to apply this synthetic strategy to metal-chalcogenide-graphene nanocompo-sites to explore efficient electrode material for Na-ion batteries-an emerging alternative to currently commercialized Li-ion batteries. What was the biggest challenge(on the way to the results presented in this paper)? Considering that the exfoliated titanate nanosheets show quite high efficiency as an additive for improving the Na-ion electrode performance of SnS 2-graphene nanocomposites, the optimal concentration of titanate additive is much lower than we expected. Thus, the biggest challenge of this work is to determine the optimal concentration of the nanosheets for enhancing the Na-ion electrode functionality of the nanocomposites. Invited for the cover of this issue is the group of Seong-Ju Hwang at the Ewha WomansU niversity.T he image depicts the criticalr ole of exfoliated metal oxide nanosheets as additivesi ni mproving the sodium-ion electrode functionality of metal-chalcogenide-graphene nanocomposites. Read the full text of the article at

The composite formation with a conductive metal sulfide domain can provide an effective methodology to improve the Na-ion electrode functionality of metal oxide. The heat treatment of TiO(B) under CS flow yields an intimately coupled TiO(B)-TiS nanocomposite with intervened TiS domain, since the reaction between metal oxide and CS leads to the formation of metal sulfide and CO. The negligible change in lattice parameters and significant enhancement of visible light absorption upon the reaction with CS underscore the formation of conductive metal sulfide domains. The resulting TiO(B)-TiS nanocomposites deliver greater discharge capacities with better rate characteristics for electrochemical sodiation-desodiation process than does the pristine TiO(B). The Na magic angle spinning nuclear magnetic resonance analysis clearly demonstrates that the electrode activities of the present nanocomposites rely on the capacitive storage of Na ions, and the TiS domains in TiO(B)-TiS nanocomposites play a role as mediators for Na ions to and from TiO(B) domains. According to the electrochemical impedance spectroscopy, the reaction with CS leads to the significant enhancement of charge transfer kinetics, which is responsible for the accompanying improvement in electrode performance. The present study provides clear evidence for the usefulness in composite formation between the semiconducting metal oxide and metal sulfide in exploring new efficient NIB electrode materials.