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Living things are a complex, coordinated network of systems, and understanding their basic organization and function integrates multiple levels of biology. This page broadly highlights our most exciting recent publications covering topics from molecular mechanisms of cellular behaviours to organismal physiology.
Cells must respond to environmental changes. In three fungal species adapted to different temperatures, cellular responses are conserved yet tuned to each organism’s thermal niche, including the formation of adaptive biomolecular condensates.
Zebrafish can regenerate after paralyzing spine injuries and regain locomotor ability, unlike mammals. Here authors show that the neurogenic factor Hb-egf promotes spinal cord regeneration in zebrafish and is regulated by an enhancer that can similarly direct expression in the pro-regenerative setting of neonatal mice.
Left-right (LR) body asymmetry is established by leftward flow in the LR organizer. Here, the authors show in Xenopus that R-Spondin 2 acts as an FGF receptor antagonist that produces a right-to-left FGF signaling gradient in response to flow to break LR symmetry.
Children’s faces resemble their parents to various degrees. Here they show that the maternal diet affects the facial appearances of newborns and that inherited and adaptive mechanisms sculpturing facial bones are linked via dietary protein levels and the mTOR signaling pathway.
Arteries are vital blood vessels for our body and their growth and patterning are critical for proper blood flow. Here they use a retina model to show that a balance of EphB4 receptor and ephrin-B2 ligand integrate a well-wired molecular network to control arteriovenous patterning and vascular growth.
The liver is segregated into spatially organized areas that serve distinct functions, though how these zones are patterned remains unclear. Here they show that mTORC1 controls spatial segregation of liver metabolic functions via modulation of Wnt signaling, and find that impaired zonation is also observed in pigs given total parenteral nutrition.
Lipid synthesis increases during the cell cycle to ensure sufficient membrane mass. Here, authors identify a lipid checkpoint in G1 phase that prevents cells from starting the cell cycle if lipid synthesis is low, thereby preventing mitotic defects.
Meiotic cells deliberately break their DNA to allow chromosomes to swap genetic material. Here, authors reveal genetically separable pathways controlling the seeding and growth of chromosome-bound protein condensates responsible for DNA breaks.
Endodermal neurogenesis is an uncommon trait among animals. Here they identify a population of endoderm-specific neural progenitor cells in the cnidarian Nematostella vectensis that is characterized by the expression of the transcription factor prdm14d.
Mitochondrial fission, performed by Drp1, is carefully regulated, particularly in neurons. Here, the authors examine Drosophila Cdk8/CDK19 function in mitochondrial fission and uncover a role phosphorylating Drp1 in the cytoplasm and show overexpression suppresses a Parkinson’s disease model.
Development of hindlimbs and external genitalia share several regulatory factors. Lozovska et al. show that Tgfbr1 controls the response to those factors; embryos lacking Tgfbr1 develop two sets of hindlimbs at the expense of the external genitalia.
ATGL is a key enzyme in intracellular lipolysis. Here, the authors use deep mutational scanning to define the determinants of protein interaction between ATGL and its regulatory partners, gaining insights into lipolysis mechanisms in cells.
Extracellular vesicles are fundamental in cellular communication. Here, authors show how C. elegans pheromones regulate vesicle production, showcasing the impact of social behaviors on cellular mechanisms.
Targeting of transport vesicles requires specific proteins and membrane lipids. Here, authors microinjected liposomes with a predetermined composition to show that targeting by SNAREs is refined when polyphosphoinositides and Rab GTPases are included.
Lysosomal storage disorders (LSDs) are severe genetic diseases currently without routine therapies. Here, the authors identified that SNX8 participates in lysosome reformation and serves as a potential drug target for new therapies to treat LSDs.
Long noncoding RNAs (lncRNAs) function in many processes yet their participation in learning is largely unknown. Here, we identify and characterize the lncRNA SLAMR, which is recruited to stimulated synapses to mediate structural plasticity during experience and fear memory consolidation.
The mechanisms regulating mitochondrial architecture in neurons remain unclear. The authors report that in dendrites, mitochondria structure is specified by the CAMKK2-AMPK pathway through compartment-specific and activity-dependent levels of fission.
Genetic association studies with affinity proteomics face challenges when dealing with protein altering variants. Suhre et al. show that nanoparticle enrichment mass-spectrometry can distinguish between epitope effects and bona fide protein quantitative traits.
Ferroptosis is a novel form of regulated cell death associated with lipid oxidation. Here, the authors demonstrate that the proferroptosis signal is activated and drives vascular aging by inducing senescence in vascular smooth muscle cells.
Lu et al. show that single-stranded DNA produced as a result of DNA damage may directly activate PprI in Deinococcus species, triggering the DNA damage response.
Spontaneous activation of VEGFRs is a hallmark of diabetes and several cancers. Here, the authors show how in VEGFR1 a juxtamembrane segment connecting the catalytic and ligand-binding domains of the receptor can prevent its spontaneous activation.
Upon physiological injury, hepatocytes transdifferentiate into biliary epithelial cells, a process involving molecular rewiring. Here, authors show that Sox4 organizes the early steps, acting as a pioneer factor to decommission hepatocyte enhancers and open chromatin around biliary genes.
The quality of germline mitochondria is essential for producing healthy oocytes. Here, Ng, Chan and Pek report a stable intron that modulates germline mitochondrial quality control during fasting, heat stress and aging.
The importance of the SEL1L-HRD1 interaction in vivo was unclear. Here, authors reported that SEL1L-HRD1 interaction is required to form a functional HRD1 ERAD complex by recruiting the E2 enzyme UBE2J1 and DERLIN to HRD1.
Actin mediates insulin secretion in pancreatic β-cells through remodeling. Here, authors report the in situ structure of actin remodeling and quantify changes in architecture, alignment, and interactions during glucose-stimulated insulin secretion.
Mitochondrial biogenesis and maintenance relies on protein import from the cytosol. Here, authors show that import failure impacts organelle structure and dynamics. They also identify a rescue mechanism involving intercellular mitochondrial transfer.
The role of methionine aminopeptidase 2 (MAP2) at the ribosome goes beyond N-terminal methionine excision. Klein et al. use cryo-EM to identify a second MAP2 binding site on the ribosome, and describe the dynamic interactions of MAP2 at the ribosome.
Succinate dehydrogenase converts malate to enoloxaloacetate, a metabolically inactive and inhibitory side product of the TCA cycle. Here, Zmuda et al. describe a conserved metabolite damage repair enzyme that can remove enol-oxaloacetate and is critical for efficient aerobic respiration.
Dysregulated autophagy and mitochondrial function are two well-described hallmarks of aging. Here, the authors describe an unexpected age-associated upregulation of mitophagy in response to neuroinflammation triggered by leaked mtDNA.
How cell cycling coordinates with cell survival and death remains unclear. Here, the authors reveal a suppressive effect of cell cycle arrest on ferroptosis and propose a ferroptosis-inducing approach to treat slow-cycling, therapy-resistant cancers.
Regulation of cell polarity is key to ensure directed cell migration. Here, Atkins et al. identify the primary cilium cAMP/cGMP ratio as a master regulator of the cell polarity of migrating cortical interneurons downstream of the CXCL12 chemokine.
Meiotic drivers of the wtf family kill progeny lacking the driver by producing a toxin and an antidote. Here, authors reveal that ubiquitination-mediated sorting of the antidote prevents it from becoming toxic and enables it to neutralize the toxin.
Different membrane proteins dynamically polarize to organize signal transduction, but the underlying mechanism is unclear. Here, the authors show that a differential diffusion mediated partitioning process is sufficient to drive such spatiotemporal patterning of membrane-associated signaling proteins.
Autophagosome formation involves membrane morphological changes. Here, authors statistically determined average shapes of forming autophagosomes from 3D electron micrographs and established a theoretical model that quantitatively reproduces them.
The cells of our bodies use chemical signals to talk with each other. Here the authors describe a class of signaling molecules called “capped peptides” that may mediate cell-cell communication. Unlike other peptides, capped peptides have unique chemical modifications which make them potentially more active and stable.
Co-fractionation mass spectrometry (CF-MS) is a powerful technique for mapping protein interactions under physiological conditions. Here, the authors uniformly re-process 411 CF-MS experiments and carry out meta-analyses of protein abundance, protein-protein interactions, and phosphorylation sites in the resulting resource.
How nuclear architecture assists the replication stress response is still largely unknown. Here the authors show that nuclear actin polymerization rapidly extends upon mild DNA damage. By limiting Primpol activity, this response mediates fork slowing and reversal, protecting chromosome stability.
Here the authors show that the basal activation of the interferon/ISG15 pathway is required for the stability of nascent DNA during replication and its upregulation promotes viability, proliferation and acquisition of drug resistance in BRCA1/2 deficient cells.
Few resident cell surface proteins have been identified at the axon initial segment. Here, Ogawa and colleagues use proximity labeling and proteomics to identify Contactin-1 as a transmembrane axon initial segment protein that regulates brain wiring.
Non-alcoholic fatty liver disease affects 25% of people worldwide. Here the authors report that spliceosome component Usp39 deletion in mice leads to spontaneous steatosis and impaired autophagy through the regulation of alternative splicing.
Mitochondrial function is essential for energy metabolism in brown adipocytes. Here, the authors show that LCN2 plays a critical role as a phosphatidic acid binding protein in phospholipid acyl chain remodeling and mitochondrial bioenergetics, influencing signaling pathway activation.
Phase separation serves to compartmentalize and concentrate cellular components to facilitate essential physiological processes. Here, the authors elucidate the role and mechanism of BuGZ-mediated phase separation in the context of gut regeneration and aging.
Proximity between mitochondria and endoplasmic reticulum regulates mitochondria fitness and is adversely affected by tissue ischemia. This work reveals that Diaphanous1-Mitofusin2 interaction regulates this proximity and impairs recovery in ischemia.
The role of the mitochondrial fusion protein OPA1 in liver function is unknown. Here, authors showed that OPA1 is dispensable in the liver, and that the mitohormesis induced by OPA1 deletion prevents liver injury and contributes to liver resiliency.
The mitochondrial phosphatase PPTC7 has previously been linked to the maintenance of mitochondrial content, but the mechanisms underlying this phenotype remain unclear. Here, the authors demonstrate that loss of Pptc7 results in metabolic defects and further suggest that PPTC7 is a regulator of receptor-mediated mitophagy.
Spatial compartmentalization is central to nuclear function. Here, the authors demonstrate that EPAC1 can enter the nucleus and regulate the transcription of a histone cluster by forming biomolecular condensates in its proximity in response to cAMP.
It is unknown how the kinetochore fibrous corona is disassembled. Here, the authors reveal that Aurora A and B kinases-mediated phosphorylation activates CENP-E, which is essential to prevent the premature removal of corona proteins by dynein.
Compartmentalization is thought to modulate metabolic flux by spatially segregating enzymes and their coupled reactants. Here, the authors show that peroxisomal compartmentalization of amino acid synthesis imposes an upper limit on compartment size.
The transient elevation in protein translation during early-adulthood in Drosophila imposes long-lasting negative impacts on future aging trajectories by triggering proteostatic dysfunction at old ages.