Rock-eating mycorrhizas: their role in plant nutrition and biogeochemical cycles

A decade ago, tunnels inside mineral grains were found that were likely formed by hyphae of ectomycorrhizal (EcM) fungi. This observation implied that EcM fungi can dissolve mineral grains. The observation raised several questions on the ecology of these ¿rock-eating¿ fungi. This review addresses the roles of these rock-eating EcM associations in plant nutrition, biogeochemical cycles and pedogenesis. Research approaches ranged from molecular to ecosystem level scales. Nutrient deficiencies change EcM seedling exudation patterns of organic anions and thus their potential to mobilise base cations from minerals. This response was fungal species-specific. Some EcM fungi accelerated mineral weathering. While mineral weathering could also increase the concentrations of phytotoxic aluminium in the soil solution, some EcM fungi increase Al tolerance through an enhanced exudation of oxalate. Through their contribution to Al transport, EcM hyphae could be agents in pedogenesis, especially podzolisation. A modelling study indicated that mineral tunnelling is less important than surface weathering by EcM fungi. With both processes taken together, the contribution of EcM fungi to weathering may be significant. In the field vertical niche differentiation of EcM fungi was shown for EcM root tips and extraradical mycelium. In the field EcM fungi and tunnel densities were correlated. Our results support a role of rock-eating EcM fungi in plant nutrition and biogeochemical cycles. EcM fungal species-specific differences indicate the need for further research with regard to this variation in functional traits

Deregulated splicing is a major mechanism of RNA-induced toxicity in Huntington's disease

Huntington's disease (HD) is caused by an expanded CAG repeat in the huntingtin (HTT) gene, translating into an elongated polyglutamine stretch. In addition to the neurotoxic mutant HTT protein, the mutant CAG repeat RNA can exert toxic functions by trapping RNA-binding proteins. While few examples of proteins that aberrantly bind to mutant HTT RNA and execute abnormal function in conjunction with the CAG repeat RNA have been described, an unbiased approach to identify the interactome of mutant HTT RNA is missing. Here, we describe the analysis of proteins that preferentially bind mutant HTT RNA using a mass spectrometry approach. We show that (I) the majority of proteins captured by mutant HTT RNA belong to the spliceosome pathway, (II) expression of mutant CAG repeat RNA induces mis-splicing in a HD cell model, (III) overexpression of one of the splice factors trapped by mutant HTT ameliorates the HD phenotype in a fly model and (VI) deregulated splicing occurs in human HD brain. Our data suggest that deregulated splicing is a prominent mechanism of RNA-induced toxicity in HD

A chemical-genetic screen reveals a mechanism of resistance to PI3K inhibitors in cancer.

Linking the molecular aberrations of cancer to drug responses could guide treatment choice and identify new therapeutic applications. However, there has been no systematic approach for analyzing gene-drug interactions in human cells. Here we establish a multiplexed assay to study the cellular fitness of a panel of engineered isogenic cancer cells in response to a collection of drugs, enabling the systematic analysis of thousands of gene-drug interactions. Applying this approach to breast cancer revealed various synthetic-lethal interactions and drug-resistance mechanisms, some of which were known, thereby validating the method. NOTCH pathway activation, which occurs frequently in breast cancer, unexpectedly conferred resistance to phosphoinositide 3-kinase (PI3K) inhibitors, which are currently undergoing clinical trials in breast cancer patients. NOTCH1 and downstream induction of c-MYC over-rode the dependency of cells on the PI3K-mTOR pathway for proliferation. These data reveal a new mechanism of resistance to PI3K inhibitors with direct clinical implications

Prion‐like proteins: from computational approaches to proteome‐wide analysis

Altres ajuts: ICREA-Academia 2020Prions are self-perpetuating proteins able to switch between a soluble state and an aggregated-and-transmissible conformation. These proteinaceous entities have been widely studied in yeast, where they are involved in hereditable phenotypic adaptations. The notion that such proteins could play functional roles and be positively selected by evolution has triggered the development of computational tools to identify prion-like proteins in different kingdoms of life. These algorithms have succeeded in screening multiple proteomes, allowing the identification of prion-like proteins in a diversity of unrelated organisms, evidencing that the prion phenomenon is well conserved among species. Interestingly enough, prion-like proteins are not only connected with the formation of functional membraneless protein-nucleic acid coacervates, but are also linked to human diseases. This review addresses state-of-the-art computational approaches to identify prion-like proteins, describes proteome-wide analysis efforts, discusses these unique proteins' functional role, and illustrates recently validated examples in different domains of life

The biophysical, molecular, and anatomical landscape of pigeon CRY4: A candidate light-based quantal magnetosensor

The biophysical and molecular mechanisms that enable animals to detect magnetic fields are unknown. It has been proposed that birds have a light-dependent magnetic compass that relies on the formation of radical pairs within cryptochrome molecules. Using spectroscopic methods, we show that pigeon cryptochrome clCRY4 is photoreduced efficiently and forms long-lived spin-correlated radical pairs via a tetrad of tryptophan residues. We report that clCRY4 is broadly and stably expressed within the retina but enriched at synapses in the outer plexiform layer in a repetitive manner. A proteomic survey for retinal-specific clCRY4 interactors identified molecules that are involved in receptor signaling, including glutamate receptor-interacting protein 2, which colocalizes with clCRY4. Our data support a model whereby clCRY4 acts as an ultraviolet-blue photoreceptor and/or a light-dependent magnetosensor by modulating glutamatergic synapses between horizontal cells and cones

Fibril-induced glutamine-/asparagine-rich prions recruit stress granule proteins in mammalian cells

Prions of lower eukaryotes are self-templating protein aggregates that replicate by converting homotypic proteins into stable, tightly packed beta-sheet–rich protein assemblies. Propagation is mediated by prion domains, low-complexity regions enriched in polar and devoid of charged amino acid residues. In mammals, compositionally similar domains modulate the assembly of dynamic stress granules (SGs) that associate via multivalent weak interactions. Dysregulation of SGs composed of proteins with prion-like domains has been proposed to underlie the formation of pathological inclusions in several neurodegenerative diseases. The events that drive prion-like domains into transient or solid assemblies are not well understood. We studied the interactors of the prototype prion domain NM of Saccharomyces cerevisiae Sup35 in its soluble or fibril-induced prion conformation in the mammalian cytosol. We show that the interactomes of soluble and prionized NM overlap with that of SGs. Prion induction by exogenous seeds does not cause SG assembly, demonstrating that colocalization of aberrant protein inclusions with SG components does not necessarily reveal SGs as initial sites of protein misfolding