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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...

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.

Neuromorphic computing, which mimics biological neural networks, can overcome the high-power and large-throughput problems of current von Neumann computing. Two-terminal memristors are regarded as promising candidates for artificial synapses, which are the fundamental functional units of neuromorphic computing systems. All-inorganic CsPbI 3 perovskite-based memristors are feasible to use in resistive switching memory and artificial synapses due to their fast ion migration. However, the ideal perovskite phase α-CsPbI 3 is structurally unstable at ambient temperature and rapidly degrades to a non-perovskite δ-CsPbI 3 phase. Here, dual-phase (Cs 3 Bi 2 I 9 ) 0.4 −(CsPbI 3 ) 0.6 is successfully fabricated to achieve improved air stability and surface morphology compared to each single phase. Notably, the Ag/polymethylmethacrylate/(Cs 3 Bi 2 I 9 ) 0.4 −(CsPbI 3 ) 0.6 /Pt device exhibits non-volatile memory functions with an endurance of ≈10 3 cycles and retention of ≈10 4 s with low operation voltages. Moreover, the device successfully emulates synaptic behavior such as long-term potentiation/depression and spike timing/widthdependent plasticity. This study will contribute to improving the structural and mechanical stability of all-inorganic halide perovskites (IHPs) via the formation of dual phase. In addition, it proves the great potential of IHPs for use in low-power non-volatile memory devices and electronic synapses.The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/adfm.201906686.femto-Joule scale. [1,2] Neuromorphic computing systems that emulate the human brain are considered promising candidates for overcoming the energy and throughput limitations of conventional von Neumann computing systems. Inspired by the human brain, neuromorphic computing systems are composed of electronic neurons and synapses, and achieve a high degree of parallelism with the physically united memory and information processing unit. Artificial synapses are fundamental functional units of neuromorphic architectures, where electrical stimuli from a pre-neuron are transmitted to a post-neuron, thereby generating updated synaptic weight (i.e., causing a conductance change in an electronic device). Notably, resistive switching (RS) memory has been actively investigated for synaptic devices due to its scalability, simple structure, fast operation speed, and low-energy consumption, which are the most important requirements for neuromorphic computing. [3,4] In the last few years, halide perovskites (HPs) with the chemical formula ABX 3 [where A is an organic or inorganic (Cs or Rb) cation, B is a divalent metal cation (Pb or Sn), and X is a halide anion (I, Cl, or Br)] have been widely investigated for RS memory and artificial synapses because of their tunable bandgaps and fast ion migration. [5][6][7] To date, organolead HPs (OHPs, A = methylammonium (MA), B = Pb, and X = I, Cl, or Br) have been successfully utilized as the active layer of memristor-based artificial synapses, emulat...