AIMP1-Derived Peptide Secreted from Hair Follicle Stem Cells Promotes Hair Growth by Activating Dermal Papilla Cells.

Hair follicle stem cells (HFSCs) and dermal papilla cells (DPCs) are crucial in the biogenesis and maintenance of hair follicles (HFs). This study demonstrated that a fragment derived from aminoacyl-tRNA synthetase-interacting multifunctional protein1 (AIMP1) secreted from HFSCs activated DPCs and maintained HF homeostasis. A histological analysis revealed that AIMP1 levels in HF decreased with hair loss.

Electromagnetic Wave Absorbing, Thermal-Conductive Flexible Membrane with Shape-Modulated FeCo Nanobelts.

Electromagnetic wave (EMW)-absorbing materials, manufactured with composites of magnetic particles, are essential for maintaining a high complex permeability and modulated permittivity for impedance matching. However, commonly available EMW-absorbing materials are unsatisfactory owing to their low complex permeability in the high-frequency band. Herein, we report a thin, flexible EMW-absorbing membrane comprising shape-modulated FeCo nanobelts/boron nitride nanoparticles, which enables enhanced complex permeability in the S, C, and X bands (2-12 GHz).

Glucose-dependent control of leucine metabolism by leucyl-tRNA synthetase 1.

Despite the importance of glucose and amino acids for energy metabolism, interactions between the two nutrients are not well understood. We provide evidence for a role of leucyl-tRNA synthetase 1 (LARS1) in glucose-dependent control of leucine usage. Upon glucose starvation, LARS1 was phosphorylated by Unc-51 like autophagy activating kinase 1 (ULK1) at the residues crucial for leucine binding.

A threonyl-tRNA synthetase-mediated translation initiation machinery.

A fundamental question in biology is how vertebrates evolved and differ from invertebrates, and little is known about differences in the regulation of translation in the two systems. Herein, we identify a threonyl-tRNA synthetase (TRS)-mediated translation initiation machinery that specifically interacts with eIF4E homologous protein, and forms machinery that is structurally analogous to the eIF4F-mediated translation initiation machinery via the recruitment of other translation initiation components. Biochemical and RNA immunoprecipitation analyses coupled to sequencing suggest that this machinery emerged as a gain-of-function event in the vertebrate lineage, and it positively regulates the translation of mRNAs required for vertebrate development.

Unique N-terminal extension domain of human asparaginyl-tRNA synthetase elicits CCR3-mediated chemokine activity.

Asparaginyl-tRNA synthetase (NRS) is not only essential in protein translation but also associated with autoimmune diseases. Particularly, patients with antibodies that recognize NRS often develop interstitial lung disease (ILD). However, the underlying mechanism of how NRS is recognized by immune cells and provokes inflammatory responses is not well-understood.

Inhibition of MUC1 biosynthesis via threonyl-tRNA synthetase suppresses pancreatic cancer cell migration.

Mucin1 (MUC1), a heterodimeric oncoprotein, containing tandem repeat structures with a high proportion of threonine, is aberrantly overexpressed in many human cancers including pancreatic cancer. Since the overall survival rate of pancreatic cancer patients has remained low for several decades, novel therapeutic approaches are highly needed. Intestinal mucin has been known to be affected by dietary threonine supply since de novo synthesis of mucin proteins is sensitive to luminal threonine concentration.

Control of leucine-dependent mTORC1 pathway through chemical intervention of leucyl-tRNA synthetase and RagD interaction.

Leucyl-tRNA synthetase (LRS) is known to function as leucine sensor in the mammalian target of rapamycin complex 1 (mTORC1) pathway. However, the pathophysiological significance of its activity is not well understood. Here, we demonstrate that the leucine sensor function for mTORC1 activation of LRS can be decoupled from its catalytic activity.

Sesquiterpene lactones and scopoletins from Waldst. & Kit. and their angiotensin I-converting enzyme inhibitory activities.

Ten compounds, including a new guaiane-type sesquiterpene lactone, were isolated from the aerial parts of . The structure of the new compound was determined to be 5-hydroxyguaia-3(4),11(13),10(14)-trien-6α,12-olide, named scoparanolide. Six known sesquiterpene lactones [estafiatone, 3β,4α-dihydroxyguaia-11(13),10(14)-dien-6α,12-olide, estafiatin, preeupatundin, 3β-hydroxycostunolide, and ludovicin B] and three known coumarin derivatives (scopoletin, scoparone, and isofraxidin) were identified by nuclear magnetic resonance and electrospray ionization mass spectroscopy.

Discovery of (S)-4-isobutyloxazolidin-2-one as a novel leucyl-tRNA synthetase (LRS)-targeted mTORC1 inhibitor.

A series of leucinol analogs were investigated as leucyl-tRNA synthetase-targeted mTORC1 inhibitors. Among them, compound 5, (S)-4-isobutyloxazolidin-2-one, showed the most potent inhibition on the mTORC1 pathway in a concentration-dependent manner. Compound 5 inhibited downstream phosphorylation of mTORC1 by blocking leucine-sensing ability of LRS, without affecting the catalytic activity of LRS.

Structural basis for full-spectrum inhibition of translational functions on a tRNA synthetase.

The polyketide natural product borrelidin displays antibacterial, antifungal, antimalarial, anticancer, insecticidal and herbicidal activities through the selective inhibition of threonyl-tRNA synthetase (ThrRS). How borrelidin simultaneously attenuates bacterial growth and suppresses a variety of infections in plants and animals is not known. Here we show, using X-ray crystal structures and functional analyses, that a single molecule of borrelidin simultaneously occupies four distinct subsites within the catalytic domain of bacterial and human ThrRSs.

Leucyl-tRNA synthetase is an intracellular leucine sensor for the mTORC1-signaling pathway.

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.

Identification of gp96 as a novel target for treatment of autoimmune disease in mice.

Heat shock proteins have been implicated as endogenous activators for dendritic cells (DCs). Chronic expression of heat shock protein gp96 on cell surfaces induces significant DC activations and systemic lupus erythematosus (SLE)-like phenotypes in mice. However, its potential as a therapeutic target against SLE remains to be evaluated.