Biology subjects

Bailly, A.

Publications and source records attributed to Bailly, A..

9 recordsLinked to original sources

bioRxiv2026

The FKBP42, TWISTED DWARF1, prioritizes auxin over brassinosteroidtransport by peptidyl-prolyl cis-trans isomerization of ABCB1

The ATP-binding cassette (ABC) transporter ABCB1 transports both auxins and the brassinosteroid brassinolide (BL). ABCB1-mediated auxin (IAA) transport depends on interaction with the FKBP42 protein TWISTED DWARF1 (TWD1), yet the mechanism underlying substrate selectivity remains unclear. Here, we confirm dual IAA and BL transport by ABCB1 and show that the two substrates compete for ABCB1-mediated transport. We demonstrate that a conserved proline residue (P1008) is required for IAA, but not BL, transport. Furthermore, we identify TWD1 as a calmodulin-activated peptidyl-prolyl cis-trans isomerase (PPIase) that selectively enhances IAA, but not BL, transport through isomerization of the E1007-P1008 peptide bond. Loss of TWD1 PPIase activity abolishes ABCB1-mediated IAA export without affecting BL transport, revealing a regulatory mechanism that prioritizes auxin over brassinosteroid transport. Cryo-EM, molecular docking, and molecular dynamics simulations of wild-type ABCB1 and the ABCB1P1008G variant suggest that the P1008 loop mediates long-range communication between the nucleotide-binding domain surface and the substrate-binding pocket, thereby providing a structural mechanism by which TWD1 modulates substrate specificity. In summary, our findings establish the structural basis of ABCB1 substrate selectivity and uncover a post-translational mechanism that selectively regulates auxin transport while preserving brassinosteroid transport. One Sentence SummaryTWD1 prioritizes ABCB1-mediated auxin over brassinosteroid transport

biochemistry↗

bioRxiv2026

High residual pesticide contamination despite contrasted feeding treatments in semi-captive bred grey partridges

Food security is one of the major ongoing global anthropic challenges, driving the intensification of agricultural systems notably through the widespread use of phyto-pharmaceutical products (PPPs). Although effective for maximizing production yields through pest control, PPP contamination is pervasive across the entire agroecosystem, raising concerns about human and non-target species exposure and health effects. Organic farming has therefore been promoted as a sustainable alternative to ensure human food security and mitigate these impacts. Yet, the pathways of PPP non-target organisms contamination are insufficiently understood. While most research has focused on ingestion as the primary route of exposure, increasing evidence suggests more complex contamination dynamics. In this study, we investigated the role of food intake in shaping PPP contamination profiles in semi-captive grey partridges (Perdix perdix). To do so, 80 birds were housed in open aviaries within an agricultural landscape and fed either conventional or organic grains over a five-month period. After drawing their PPP blood profiles at the end of the exposure period, we assessed their loads and compared the pesticide prevalence and abundance between food treatments. We found similar quantity and diversity of PPP residues in blood from conventionally- and organically-fed partridges, with few differences in specific PPP compounds. Overall, these findings suggest that food intake is not necessarily the only source of contamination for non-target organisms, with alternative pathways (e.g., inhalation, dermal contact, soil and water exposure) likely playing a substantial role. Integrating multi-pathway contamination monitoring across trophic levels within a One Health framework would now be essential to better understand and mitigate PPP contamination risks.

ecology↗

bioRxiv2025

Field-based evidence of sperm quality impairment associated with conventional farming in two passerine birds.

The detrimental effects of conventional farming on bird biodiversity are increasingly documented. Despite this, the specific impacts of both organic and conventional farming practices on bird coloration and sperm quality in natural settings remain unexplored. This study aimed to determine whether these farming practices differentially affect body mass, coloration intensity, and sperm quality in passerine birds inhabiting agricultural landscapes. We captured seven passerine species in hedgerows adjacent to fields farmed organically or conventionally, within a 250-meter radius representative of their breeding home ranges. Body mass was measured across all species, and an index of coloration intensity, based on carotenoid (yellow/orange) and melanin (black) pigments, was assessed in four species. Additionally, we evaluated three sperm quality parameters (sperm density, percentage of abnormal sperm, and intra-individual variance of sperm morphology) using fresh sperm samples collected from four species in the field. We hypothesized that birds living near conventional fields would exhibit lower body mass due to reduced food availability. Additionally, we predicted that the more favourable conditions associated with organic farming, such as greater food abundance and lower exposure to pollutants, would benefit birds, leading to enhanced coloration and improved sperm quality. Our results did not reveal any difference in body mass or coloration. The absence of observable effects might be due to several factors: methodological limitations, cross-contamination between habitats or insufficient exposure to farming practices that may hide any potential difference between the two habitats, or the intrinsic adaptive strategies of the species. However, subgroup analysis of three and four species revealed a decrease in sperm density and a higher proportion of abnormal spermatozoa in the Common Whitethroat and Common Nightingale living in conventional farming, respectively. Although our sample size was limited, we believe these findings highlight the potential negative effects of conventional farming on birds.

ecology↗

bioRxiv2023

Two distinct mechanisms lead to either oocyte or spermatocyte decrease in C. elegans after whole developmental exposure to gamma-rays

Wildlife is subject to various sources of pollution, including ionizing radiation. Adverse effects can impact organisms survival, growth, or reproduction, later affecting population dynamics. In invertebrates, reproduction, which directly impacts population dynamics, has been found to be the most radiosensitive endpoint. Understanding the underlying molecular pathways inducing this reproduction decrease can help to comprehend species-specific differences in radiosensitivity. In line with previous studies, we used a life stage dependent approach to better understand the molecular determinants of reproduction decrease, especially of gamete decrease, in the hermaphrodite roundworm Caenorhabditis elegans. Worms were chronically exposed to 50 mGy{middle dot}h-1 external gamma ionizing radiations throughout different developmental periods (namely embryogenesis, gametogenesis, and full development). Conserved molecular pathways across invertebrates and vertebrates involved in reproduction processes and stress response were analyzed: apoptosis and MAP kinase Ras/ERK (MPK-1). Our results showed that these pathways are life-stage dependant, resulting from an accumulation of damages upon chronic exposure to IR throughout the whole development. The Ras/ERK pathway was found to be activated in our conditions in the pachytene region of the gonad where it induces the apoptotic pathway, but not in the ovulation zone, showing no incidence on oocyte maturation and ovulation. Additionally, no effect on germ cell proliferation was found, meaning that Ras/ERK pathway is probably not involved in this process in our conditions. Finally, a functional analysis of apoptosis revealed that the decrease of ovulation rate is due to DNA-damaged induced apoptosis which does not occur in spermatocytes. Thus, sperm decrease seem to be mediated via another mechanism, probably a decrease in germ cells proliferation speed that needs further investigation to better characterize sex-specific responses to IR exposure.

pharmacology and toxicology↗

bioRxiv2023

Targeting the deNEDDylating enzyme NEDP1 to ameliorate ALS phenotypes through Stress Granules dissolution

In Amyotrophic Lateral Sclerosis (ALS) motor neuron disease, mutations in proteins that upon stress localize within cytoplasmic protein inclusions called Stress Granules (SGs), are linked to the formation of aberrant inclusions, which are related to neuronal cell death. By combining studies in human cells and C. elegans including the use of Nanobodies, we found that inhibition of NEDP1, the enzyme responsible for the processing and deconjugation of the Ubiquitin-like molecule NEDD8 from substrates, promotes the elimination both of physiological and pathological SGs. The hyper-NEDDylation of Poly-(ADP-ribose) polymerase-1 enzyme upon NEDP1 inhibition compromises PAR production and is a key mechanism for the observed SG phenotype. Importantly, the above-described effects are related to improved cell survival in human cells, and in C. elegans, NEDP1 deletion ameliorates ALS-phenotypes related to animal motility. Our studies reveal NEDP1 as potential therapeutic target for ALS, based on the elimination of aberrant SGs.

cell biology↗

bioRxiv2022

A key residue of plant ABC transporter modulates access path geometry and phenylpropanoid substrate selectivity

ABCG46 of the legume Medicago truncatula is an ABC-type transporter responsible for highly selective translocation of the phenylpropanoids, 4-coumarate and liquiritigenin, over the plasma membrane. To investigate molecular determinants of the observed substrate selectivity, we applied a combination of phylogenetic and biochemical analyses, AlphaFold2 structure prediction, molecular dynamics simulations, and mutagenesis. We discovered an unusually narrow transient access path to the central cavity of MtABCG46 that constitutes an initial filter responsible for the selective translocation of these phenylpropanoids through a lipid bilayer. Furthermore, we identified remote residue F562 as pivotal for maintaining the stability of this filter. The determination of individual amino acids that impact the selective transport of specialized metabolites may provide new opportunities associated with ABCGs being of interest, as a clinically relevant group of proteins.

biochemistry↗

bioRxiv2020

Cooperation between Caenorhabditis elegans COMPASS and condensin in germline chromatin organization

Deposition of histone H3 lysine 4 (H3K4) methylation at promoters by SET1/COMPASS is associated with context-dependent effects on gene expression and local changes in chromatin organization. Whether SET1/COMPASS also contributes to higher-order chromosome structure has not been investigated. Here, we address this question by quantitative FRET (Forster resonance energy transfer)-based fluorescence lifetime imaging microscopy (FLIM) on C. elegans germ cells expressing histones H2B-eGFP and H2B-mCherry. We find that SET1/COMPASS subunits strongly influence meiotic chromosome organization, with marked effects on the close proximity between nucleosomes. We further show that inactivation of SET-2, the C. elegans homologue of SET1, or CFP-1, the chromatin targeting subunit of COMPASS, strongly enhance chromosome organization defects and loss of fertility resulting from depletion of condensin-II. Defects in chromosome morphology resulting from conditional inactivation of topoisomerase II, another structural component of chromosomes, were also aggravated in the absence of SET-2. Combined, our in vivo findings suggest a model in which the SET1/COMPASS histone methyltransferase complex plays a role in shaping meiotic chromosome in cooperation with the non-histone proteins condensin-II and topoisomerase.

genetics↗

bioRxiv2020

A conserved D/E-P motif in the nucleotide binding domain of plant ABCB/PGP-type ABC transporters defines their auxin transport capacity

Auxin transport activity of ABCB1 was suggested to be regulated by physical interaction with the FKBP42/Twisted Dwarf1 (TWD1), a bona fide peptidylprolyl cis-trans isomerase (PPIase), but all attempts to demonstrate such a PPIase activity on TWD1 have failed so far. By using a structure-based approach we have identified a series of surface-exposed proline residues in the C-terminal nucleotide binding fold and linker of Arabidopsis ABCB1 that do not alter ABCB1 protein stability or location but its catalytic transport activity. P1.008 was uncovered as part of a conserved signature D/E-P motif that seems to be specific for Auxin-Transporting ABCBs, we now refer to as ATAs. Beside the proline, also mutation of the acidic moiety prior to the proline abolishes auxin transport activity by ABCB1. So far, all higher plant ABCBs for that auxin transport was safely proven carry this conserved motif underlining its diagnostic potential. Introduction of this D/E-P motif into malate importer, ABCB14, increases both its malate and its background auxin transport activity, suggesting that this motif has an impact on transport capacity. The D/E-P1.008 motif is also important for ABCB1-TWD1 interaction and activation of ABCB1-mediated auxin transport by TWD1, supporting a scenario in that TWD1 acts as an activator of ABCB1 transport activity by means of its PPIase. In summary, our data imply a dual function for TWD1 acting as an ABCB co-chaperone required for ABCB biogenesis and as a putative activator of ABCB-mediated auxin transport by cis-trans isomerization of peptidyl-prolyl bonds.

biochemistry↗

bioRxiv2019

The NEDD8 cycle controlled by NEDP1 upon DNA damage is a regulatory module of the HSP70 ATPase activity

Ubiquitin and ubiquitin-like chains are finely balanced by the action of conjugating and de-conjugating enzymes. Alterations in this balance trigger signalling events required for the response to stress conditions and are often observed in pathologies. How such changes are detected is not well-understood. We show that upon DNA damage the induction of the de-NEDDylating enzyme NEDP1 restricts the formation of poly-NEDD8 chains, mainly through lysines K11/K48. This promotes APAF1 oligomerisation and apoptosis induction, a step that requires the HSP70 ATPase activity. We found that HSP70 binds to NEDD8 and in vitro, mono-NEDD8 stimulates the ATPase activity of HSP70, counteracted upon poly-NEDDylation. This effect is independent of NEDD8 conjugation onto substrates. The studies identify the HSP70 chaperone as sensor of changes in the NEDD8 cycle, providing mechanistic insights for a cytoplasmic role of NEDD8 in the DNA damage induced apoptosis. They also indicate that the balance between mono- versus poly-NEDDylation is a regulatory module of HSP70 function. The above findings may be important in tumorigenesis, as we find that NEDP1 levels are downregulated in Hepatocellular Carcinoma with concomitant accumulation of NEDD8 conjugates.

molecular biology↗