RESUMEN
The decidual-placental interface is one of the most diverse and rapidly evolving tissues in mammals. Its origin as a chimeric fetal-maternal tissue poses a unique evolutionary puzzle. We present single-cell RNA sequencing atlases from the fetal-maternal interfaces of the opossum, a marsupial, the Malagasy common tenrec, an afrotherian with primitive reproductive features, and mouse, guinea pig, and human. Invasive trophoblast shares a common transcriptomic signature across eutherians, which we argue represents a cell type family that radiated following the evolution of hemochorial placentation. We find evidence that the eutherian decidual stromal cell evolved stepwise from a predecidual state retained in Tenrec , followed by a second decidual cell type originating in Boreoeutheria with endocrine characteristics. We reconstruct ligand-receptor signaling to test evolutionary hypotheses at scale. Novel trophoblast and decidual cell types display strong integration into signaling networks compared to other cells. Additionally, we find consistent disambiguation between fetal and maternal signaling. Using phylogenetic analysis, we infer the cell-cell signaling network of the Placental common ancestor, and identify increased rates of signaling evolution in Euarchontoglires. Together, our findings reveal novel cell type identities and cell signaling dynamics at the mammalian fetal-maternal interface.
RESUMEN
The common human SNP rs3820282 is associated with multiple phenotypes including gestational length and likelihood of endometriosis and cancer, presenting a paradigmatic pleiotropic variant. Deleterious pleiotropic mutations cause the co-occurrence of disorders either within individuals, or across population. When adverse and advantageous effects are combined, pleiotropy can maintain high population frequencies of deleterious alleles. To reveal the causal molecular mechanisms of this pleiotropic SNP, we introduced this substitution into the mouse genome by CRISPR/Cas 9. Previous work showed that rs3820282 introduces a high-affinity estrogen receptor alpha-binding site at the Wnt4 locus. Here, we show that this mutation upregulates Wnt4 transcription in endometrial stroma, following the preovulatory estrogen peak. Effects on uterine transcription include downregulation of epithelial proliferation and induction of progesterone-regulated pro-implantation genes. We propose that these changes increase uterine permissiveness to embryo invasion, whereas they decrease resistance to invasion by cancer and endometriotic foci in other estrogen-responsive tissues.
Asunto(s)
Endometriosis , Neoplasias , Embarazo , Femenino , Humanos , Animales , Ratones , Endometriosis/genética , Endometriosis/metabolismo , Alelos , Endometrio/metabolismo , Estrógenos/metabolismo , Neoplasias/genética , Proteína Wnt4/genéticaRESUMEN
BACKGROUND: The plant immune system is innate and encoded in the germline. Using it efficiently, plants are capable of recognizing a diverse range of rapidly evolving pathogens. A recently described phenomenon shows that plant immune receptors are able to recognize pathogen effectors through the acquisition of exogenous protein domains from other plant genes. RESULTS: We show that plant immune receptors with integrated domains are distributed unevenly across their phylogeny in grasses. Using phylogenetic analysis, we uncover a major integration clade, whose members underwent repeated independent integration events producing diverse fusions. This clade is ancestral in grasses with members often found on syntenic chromosomes. Analyses of these fusion events reveals that homologous receptors can be fused to diverse domains. Furthermore, we discover a 43 amino acid long motif associated with this dominant integration clade which is located immediately upstream of the fusion site. Sequence analysis reveals that DNA transposition and/or ectopic recombination are the most likely mechanisms of formation for nucleotide binding leucine rich repeat proteins with integrated domains. CONCLUSIONS: The identification of this subclass of plant immune receptors that is naturally adapted to new domain integration will inform biotechnological approaches for generating synthetic receptors with novel pathogen "baits."
Asunto(s)
Fusión Génica , Sitios Genéticos , Proteínas NLR/genética , Proteínas de Plantas/genética , Poaceae/genética , Poaceae/inmunología , Receptores Inmunológicos/genética , Secuencias de Aminoácidos , Cromosomas de las Plantas , Duplicación de Gen , Genes de Plantas , Proteínas NLR/química , Filogenia , Proteínas de Plantas/química , Poaceae/clasificación , Dominios Proteicos/genética , Receptores Inmunológicos/química , Sintenía , Translocación GenéticaRESUMEN
BACKGROUND: Plants deploy immune receptors to detect pathogen-derived molecules and initiate defense responses. Intracellular plant immune receptors called nucleotide-binding leucine-rich repeat (NLR) proteins contain a central nucleotide-binding (NB) domain followed by a series of leucine-rich repeats (LRRs), and are key initiators of plant defense responses. However, recent studies demonstrated that NLRs with non-canonical domain architectures play an important role in plant immunity. These composite immune receptors are thought to arise from fusions between NLRs and additional domains that serve as "baits" for the pathogen-derived effector proteins, thus enabling pathogen recognition. Several names have been proposed to describe these proteins, including "integrated decoys" and "integrated sensors". We adopt and argue for "integrated domains" or NLR-IDs, which describes the product of the fusion without assigning a universal mode of action. RESULTS: We have scanned available plant genome sequences for the full spectrum of NLR-IDs to evaluate the diversity of integrations of potential sensor/decoy domains across flowering plants, including 19 crop species. We manually curated wheat and brassicas and experimentally validated a subset of NLR-IDs in wild and cultivated wheat varieties. We have examined NLR fusions that occur in multiple plant families and identified that some domains show re-occurring integration across lineages. Domains fused to NLRs overlap with previously identified pathogen targets confirming that they act as baits for the pathogen. While some of the integrated domains have been previously implicated in disease resistance, others provide new targets for engineering durable resistance to plant pathogens. CONCLUSIONS: We have built a robust reproducible pipeline for detecting variable domain architectures in plant immune receptors across species. We hypothesize that NLR-IDs that we revealed provide clues to the host proteins targeted by pathogens, and that this information can be deployed to discover new sources of disease resistance.
Asunto(s)
Enfermedades de las Plantas/inmunología , Inmunidad de la Planta , Proteínas de Plantas/inmunología , Plantas/inmunología , Secuencia de Aminoácidos , Resistencia a la Enfermedad , Fusión Génica , Interacciones Huésped-Patógeno , Datos de Secuencia Molecular , Filogenia , Enfermedades de las Plantas/microbiología , Proteínas de Plantas/química , Proteínas de Plantas/genética , Plantas/química , Plantas/genética , Plantas/microbiología , Estructura Terciaria de Proteína , Triticum/química , Triticum/genética , Triticum/inmunología , Triticum/microbiologíaRESUMEN
Intracellular transport is mediated by molecular motors that bind cargo to be transported along the cytoskeleton. Here, we report, for the first time, that peroxisomes (POs), lipid droplets (LDs), and the endoplasmic reticulum (ER) rely on early endosomes (EEs) for intracellular movement in a fungal model system. We show that POs undergo kinesin-3- and dynein-dependent transport along microtubules. Surprisingly, kinesin-3 does not colocalize with POs. Instead, the motor moves EEs that drag the POs through the cell. PO motility is abolished when EE motility is blocked in various mutants. Most LD and ER motility also depends on EE motility, whereas mitochondria move independently of EEs. Covisualization studies show that EE-mediated ER motility is not required for PO or LD movement, suggesting that the organelles interact with EEs independently. In the absence of EE motility, POs and LDs cluster at the growing tip, whereas ER is partially retracted to subapical regions. Collectively, our results show that moving EEs interact transiently with other organelles, thereby mediating their directed transport and distribution in the cell.
Asunto(s)
Citoesqueleto/metabolismo , Retículo Endoplásmico/metabolismo , Endosomas/metabolismo , Gotas Lipídicas/metabolismo , Peroxisomas/metabolismo , Dineínas/metabolismo , Proteínas Fluorescentes Verdes/química , Cinesinas/metabolismo , Lípidos/química , Microtúbulos/metabolismo , Mitocondrias/metabolismo , Datos de Secuencia Molecular , Mutación , Transporte de Proteínas , Saccharomyces cerevisiae , UstilagoRESUMEN
To cause rice blast disease, the fungus Magnaporthe oryzae develops a pressurized dome-shaped cell called an appressorium, which physically ruptures the leaf cuticle to gain entry to plant tissue. Here, we report that a toroidal F-actin network assembles in the appressorium by means of four septin guanosine triphosphatases, which polymerize into a dynamic, hetero-oligomeric ring. Septins scaffold F-actin, via the ezrin-radixin-moesin protein Tea1, and phosphatidylinositide interactions at the appressorium plasma membrane. The septin ring assembles in a Cdc42- and Chm1-dependent manner and forms a diffusion barrier to localize the inverse-bin-amphiphysin-RVS-domain protein Rvs167 and the Wiskott-Aldrich syndrome protein Las17 at the point of penetration. Septins thereby provide the cortical rigidity and membrane curvature necessary for protrusion of a rigid penetration peg to breach the leaf surface.