Amino acids are required for activation of the mammalian target of rapamycin (mTOR) kinase, which regulates protein translation, cell size, and autophagy. However, the amino acid sensor that directly couples intracellular amino acid-mediated signaling to mTORC1 is unknown. Here we show that leucyl-tRNA synthetase (LRS) plays a critical role in amino acid-induced mTORC1 activation by sensing intracellular leucine concentration and initiating molecular events leading to mTORC1 activation. Mutation of LRS amino acid residues important for leucine binding renders the mTORC1 pathway insensitive to intracellular levels of amino acids. We show that LRS directly binds to Rag GTPase, the mediator of amino acid signaling to mTORC1, in an amino acid-dependent manner and functions as a GTPase-activating protein (GAP) for Rag GTPase to activate mTORC1. This work demonstrates that LRS is a key mediator for amino acid signaling to mTORC1.

Spintronic devices based on magnetic skyrmions are a promising candidate for nextgeneration memory applications due to their nanometre-size, topologically-protected stability and efficient current-driven dynamics. Since the recent discovery of roomtemperature magnetic skyrmions, there have been reports of current-driven skyrmion displacement on magnetic tracks and demonstrations of current pulse-driven skyrmion generation. However, the controlled annihilation of a single skyrmion at room temperature has remained elusive. Here we demonstrate the deterministic writing and deleting of single isolated skyrmions at room temperature in ferrimagnetic GdFeCo films with a device-compatible stripline geometry. The process is driven by the application of current pulses, which induce spin-orbit torques, and is directly observed using a time resolved nanoscale X-ray imaging technique. We provide a current-pulse profile for the efficient and deterministic writing and deleting process. Using micromagnetic simulations, we also reveal the microscopic mechanism of the topological fluctuations that occur during this process.Nanoscale memory devices that employ magnetic materials and offer non-volatility and efficient electrical controllability have the potential to outperform and eventually replace conventional silicon-based memory technologies such as DRAM or NAND-Flash 1-3 . Among the many different types of spintronic memory devices available, those based on magnetic skyrmions -topologically non-trivial spin nanostructures -are of particular interest. 4-10 Key advantages of skyrmion-based memory device include their stability 9 , high-density arrangement 4,5 and low-power operation using electrical excitations 6-8 . Recently the room-temperature stabilization of magnetic skyrmions and their current pulse-induced displacement on nanotracks has been reported in magnetic heterostructures such as Ta/CoFeB/MgO 11,12 , Pt/Co/Ta 13 , Pt/CoFeB/MgO 13-15 , Pt/Co/Ir 16 and Pt/GdFeCo/MgO 17 where the strong interfacial Dzyaloshinskii-Moriya interaction (DMI)leads to the stabilization of the skyrmion structures 18,19 . While such current-controlled skyrmion motion is applicable to an actual device scheme, the deterministic writing and deleting of a single isolated magnetic skyrmion at room temperature is required for fully functional skyrmionic devices 10,20 .Theoretical studies have suggested that skyrmions can be created by applying localized vertical spin-polarized current to a confined geometry 21 or well-defined notches 22 .Moreover, there are suggestions that a single skyrmion can be formed by the conversion of a pair of domain walls 23,24 . However, the controlled creation of a single skyrmion, and the subsequent annihilation of the same skyrmion, has only been experimentally achieved at low temperatures with spin-polarized scanning tunneling microscopy (SP-STM) 8,25 . This approach requires the in situ deposition of material at cryogenic conditions, which may be hard to incorporate into actual commercial devices. Recently, several s...

Although adaptive systems of immunity against tumor initiation and destruction are well investigated, less understood is the role, if any, of endogenous factors that have conventional functions. Here we show that glycyl-tRNA synthetase (GRS), an essential component of the translation apparatus, circulates in serum and can be secreted from macrophages in response to Fas ligand that is released from tumor cells. Through cadherin (CDH)6 (K-cadherin), GRS bound to different ERK-activated tumor cells, and released phosphatase 2A (PP2A) from CDH6. The activated PP2A then suppressed ERK signaling through dephosphorylation of ERK and induced apoptosis. These activities were inhibited by blocking GRS with a soluble fragment of CDH6. With in vivo administration of GRS, growth of tumors with a high level of CDH6 and ERK activation were strongly suppressed. Our results implicate a conventional cytoplasmic enzyme in translation as an intrinsic component of the defense against ERK-activated tumor formation.A s ancient proteins that arose as part of the development of the genetic code, aminoacyl-tRNA synthetases (AARSs) are essential components of the translation apparatus. The 20 enzymes, 1 for each amino acid, catalyze the attachment of each amino acid to its cognate tRNA in the cytoplasm, where the charged tRNAs are then used for ribosomal protein synthesis (1). Surprisingly, ex-translational functions have been discovered for many tRNA synthetases, including gene regulation in Escherichia coli, RNA splicing in mitochondria of Neurospora crassa (2), and a diverse variety of functions in vertebrates that include among others regulation of inflammatory responses and of angiogenesis (3). These expanded functions are associated with the accretive additions of specialized motifs and domainssuch as internal short sequence motifs and appended GST, leucine zipper, and helix-turn-helix domains (4). The specialized motif and domain additions facilitate new protein-protein interactions that confer novel functions. Some of the many disease connections to AARSs, and to proteins that are part of the multi-tRNA synthetase complex in mammalian cells, are thought to result from disruptions to, or alterations of, their ex-translational functions (5, 6). Indeed, there are dominant CharcotMarie-Tooth disease-causing mutations in tyrosyl-and glycyltRNA synthetases that do not disrupt aminoacylation activity (7,8).Also surprising for essential components of the translation apparatus was the observation that specific fragments (produced by alternative splicing or natural proteolysis) of tyrosyl-and tryptophanyl-tRNA synthetases (YRS and WRS) bind to and signal through extracellular receptors, including chemokine receptor 1 and 2 (CXCR1 and -2) on polymorphonuclear leukocyte (PMN) cells (YRS) (9) and vascular endothelial (VE)-cadherin on endothelial cells (WRS) (10). These two synthetases are secreted from mammalian cells under specific conditions that potentiate their ex-translational functions (11, 12). Collectively, these observations raised th...

Lead sulfide (PbS) quantum dots (QDs) have great potential in optoelectronic applications because of their desirable characteristics as a light absorber for near-infrared (NIR) photodetection. However, most PbS-based NIR photodetectors are two-terminal devices, which require an integrated pixel circuit to be practical photosensors. Here we report on PbS QD/indium gallium zinc oxide (InGaZnO, IGZO) metal oxide semiconductor hybrid phototransistors with a photodetection capability between 700 and 1400 nm, a range that neither conventional Si nor InGaAs photodetectors can cover. The new hybrid phototransistor exhibits excellent photoresponsivity of over 10 6 A W − 1 and a specific detectivity in the order of 10 13 Jones for NIR (1000 nm) light. Furthermore, we demonstrate an NIR (1300 nm) imager using photogating inverter pixels based on PbS/IGZO phototransistors at an imaging frequency of 1 Hz with a high output voltage photogain of~4.9 V (~99%). To the best of our knowledge, this report demonstrates the first QD/metal oxide hybrid phototransistor-based flat panel NIR imager. Our hybrid approach using QD/metal oxide paves the way for the development of gate-tunable and highly sensitive flat panel NIR sensors/ imagers that can be easily integrated.

Lysyl-tRNA synthetase (KRS) can be released from cancer cells to cause inflammation, but the mechanism of KRS secretion is unknown. Kim et al. demonstrate that KRS is cleaved by caspase-8, which exposes a binding motif for syntenin and facilitates the secretion of KRS in exosomes.