Biology subjects

Cuello, C.

Publications and source records attributed to Cuello, C..

3 recordsLinked to original sources

bioRxiv2025

Overexpression of the sugar transporter VvHT5 turns grapevine into a better host for Botrytis cinerea

Sugars are key modulators of plant-pathogen interactions, serving both as metabolic resources and as signaling molecules that influence defense outcomes. In grapevine (Vitis vinifera), the hexose transporter VvHT5, an ortholog of Arabidopsis thaliana STP13, is strongly induced during fungal infections, suggesting a role in defense-related sugar partitioning. Here, we examined the function of VvHT5 in grapevine susceptibility to the necrotrophic fungus Botrytis cinerea. Transgenic lines overexpressing VvHT5 were generated in two cultivars, Thompson Seedless and Chardonnay, and displayed increased sugar uptake in leaves. Upon B. cinerea inoculation, these lines exhibited enhanced lesion development and fungal proliferation, contrasting with the tolerance phenotype previously observed in A. thaliana expressing VvHT5. Dual RNA-seq analysis revealed that VvHT5 overexpression triggers a transcriptional landscape favoring carbohydrate metabolism, cell wall remodeling, and attenuation of defense responses, paralleled by upregulation of fungal genes involved in sugar acquisition and virulence. These results demonstrate that while VvHT5 contributes to restricting sugar availability to pathogens in Arabidopsis, its constitutive activation in grapevine enhances host suitability for B. cinerea. Our findings highlight the complexity of sugar-mediated interactions and underscore the importance of host context in determining the outcome of plant-pathogen competition for carbon resources. HIGHLIGHTSO_LIVvHT5 overexpression increases Botrytis cinerea susceptibility in grapevine C_LIO_LIDual RNA-seq uncovers coordinated transcriptional shifts in host and pathogen C_LIO_LIVvHT5 reprograms sugar partitioning and defense-associated metabolism C_LIO_LIContrasting STP13-like responses between grapevine and Arabidopsis C_LIO_LISugar uptake activity of VvHT5 promotes fungal access to host carbon C_LI

plant biology↗

bioRxiv2024

Genome-based discovery of pachysiphine synthases in Tabernaemontana elegans

Plant specialized metabolism represents an inexhaustible source of active molecules, some of which have been used in human health for decades. Among these, monoterpene indole alkaloids (MIAs) include a wide range of valuable compounds with anticancer, antihypertensive, or neuroactive properties. This is particularly the case for the pachysiphine derivatives which show interesting antitumor and anti-alzheimer activities but accumulate at very low levels in several Tabernaemontana species. Unfortunately, genome data in Tabernaemontanaceae are lacking and knowledge on the biogenesis of pachysiphine-related MIAs in planta remains scarce, limiting the prospects for biotechnological supply of many pachysiphine-derived biopharmaceuticals. Here, we report a raw version of the toad tree (Tabernaemontana elegans) genome sequence. These new genomic resources led to the identification and characterization of a couple of genes encoding cytochrome P450 with pachysiphine synthase activity. Our phylogenomic and docking analyses highlights the different evolutionary processes that have been recruited to epoxidize the pachysiphine precursor tabersonine at a specific position and in a dedicated orientation, thus enriching our understanding of the diversification and speciation of the MIA metabolism in plants. These gene discoveries also allowed us to engineer the synthesis of MIAs in yeast through the combinatorial association of metabolic enzymes resulting in the tailor-made synthesis of non-natural MIAs. Overall, this work represents a step forward for the future supply of pachysiphine-derived drugs by microbial cell factories. Significance StatementWhile pachysiphine is a monoterpene indole alkaloid of high interest and the precursor of an anti-Alzheimer compound, its biosynthesis involving the epoxidation of tabersonine remains uncharacterized. By sequencing and assembling the genome of Tabernaemontana elegans, we identified two P450s exhibiting a pachysiphine synthase activity that we modelized to explore the evolutionary scenario leading to the acquisition of this expoxidase activity; and used to engineer yeast cell factories for securing pachysiphine supply and producing new-to-nature alkaloids.

plant biology↗

bioRxiv2018

Methyl-CpG binding domain 2 (Mbd2) deficiency causes cognitive, social and emotional functional deficits

The Methyl-CpG-Binding Domain Protein family has been implicated in neurodevelopmental disorders. The Methyl-CpG-binding domain 2 (Mbd2) binds methylated DNA and was shown to play an important role in cancer and immunity. Some evidence linked this protein to neurodevelopment. However, its exact role in neurodevelopment and brain function is mostly unknown. Here we show that Mbd2-deficiency in mice (Mbd2-/-) results in deficits in cognitive, social and emotional functions. Mbd2 binds regulatory DNA regions of neuronal genes in the hippocampus and loss of Mbd2 alters the expression of hundreds of genes with a robust down-regulation of neuronal gene pathways. Further, a genome-wide DNA methylation analysis found an altered DNA methylation pattern in regulatory DNA regions of neuronal genes in Mbd2-/- mice. Differentially expressed genes significantly overlap with gene-expression changes observed in brains of Autism Spectrum Disorder (ASD) individuals. Notably, down-regulated genes are significantly enriched for human ortholog ASD risk-genes. Observed hippocampal morphological abnormalities were similar to those found in individuals with ASD and ASD rodent models. Hippocampal Mbd2 knockdown partially recapitulates the behavioral phenotypes observed in Mbd2-/- mice. These findings suggest Mbd2 is a novel epigenetic regulator of genes that are associated with ASD in humans. Mbd2 loss causes behavioral alterations that resemble those found in ASD individuals.

neuroscience↗