Biology subjects

Jordan, F.

Publications and source records attributed to Jordan, F..

9 recordsLinked to original sources

bioRxiv2026

A phosphorylation-dependent mechanism controls splice variant-specific S-palmitoylation of cardiac Kv4.3

S-palmitoylation modulates the activity of many cardiac ion channels, yet the upstream signals that control this post-translational modification (PTM) are poorly defined. Here we identify a phosphorylation-dependent mechanism that governs splice variant-specific S-palmitoylation of the potassium channel Kv4.3. Using Acyl-RAC in native tissue and heterologous cells, we map palmitoylation to C546/547 in the intrinsically disordered Kv4.3 C-terminal tail. The short Kv4.3 splice variant Kv4.3S is [~]2.5-3-fold more palmitoylated than the long splice variant Kv4.3L, and systematic mutagenesis localises the dominant inhibitory determinant of Kv4.3 S-palmitoylation to residues 488-498 within the Kv4.3L-specific splice insert. KChIP2.1 promotes accumulation of a post-translationally modified Kv4.3 species that is selectively S-palmitoylated, and nanobody-targeted dephosphorylation removes this species and reduces Kv4.3 S-palmitoylation. Phos-tag electrophoresis and C-terminal truncation mapping identify S538 as the principal phosphorylation site enabling Kv4.3 S-palmitoylation; mutation of S538 markedly reduces formation of the palmitoylation-competent species. TurboID proximity-labelling and biochemical assays indicate that phosphorylation enhances recruitment of Kv4.3 to zDHHC5. Acute kinase inhibition rapidly eliminates phosphorylation but only gradually reduces palmitoylation, revealing temporal uncoupling between these PTMs. Functionally, non-palmitoylatable Kv4.3S exhibits larger peak currents, faster inactivation, and a left-shifted activation curve, consistent with palmitoylation limiting channel function and modulating gating transitions. Together, these findings identify phosphorylation of S538 as a priming modification that licenses Kv4.3 S-palmitoylation at C546/547, explain splice-variant differences in S-palmitoylation, and define a PTM cascade that tunes Kv4.3 channel behaviour.

cell biology↗

bioRxiv2024

Effects of joint invasion: how co-invaders affect each other's success in model food webs?

While there is considerable research on interactions between invasive and native species, as well as on the impact of invasive species on the resident community, less focus has been placed on exploring the relationship and interactions among invasive species themselves. Nevertheless, it is widely acknowledged that invasive species can have either positive or negative effects on one anothers success, in addition to neutral outcomes. In the present theoretical study, we compared the success of two invasive non-native species in two scenarios: when they invaded the resident food web separately and simultaneously. We investigated the correlations between their direct and indirect ecological relationships and the topological positions of them in the food web, with the varying outcomes of joint invasion. Using the allometric bioenergetic model (ABM) for dynamical simulations, we detected the success of invasion (presence or absence of invaders) and the direction of their biomass change comparing separated and simultaneous invasion scenarios. We studied the relationships among these variables after detailed numerical simulations with variable key parameters of the model. We found that direct and indirect ecological relationships between the two invaders are significantly modifies the invasion scenarios: the predator-prey relationship increases the probability of invasion success for both invaders, but the equilibrium biomass of at least one of them is more likely to be reduced than in separate invasions. The trophic cascade or competitive relationship between them during simultaneous invasion also affects their success rate, with the former having a positive effect and the latter a negative one. Further, we found that higher trophic level and lower betweenness centralities of the invaders reduces the likelihood of invasion success regardless of the presence or absence of another invasive species. The results of the study can be tested experimentally in micro- and mesocosms. HIGHLIGHTSO_LIIn a joint invasion, invaders can influence each others success C_LIO_LIPredator-prey relationships between invaders increase the joint invasion success C_LIO_LICompetition increases the failure of at least one invader C_LIO_LIThe trophic cascade between invaders increases the joint invasion success C_LIO_LIHigher trophic levels or lower betweenness centralities of the invaders increase the probability of unsuccessful joint invasion C_LI GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=140 SRC="FIGDIR/small/573872v1_ufig1.gif" ALT="Figure 1"> View larger version (63K): org.highwire.dtl.DTLVardef@1b3638eorg.highwire.dtl.DTLVardef@4d1f47org.highwire.dtl.DTLVardef@1409573org.highwire.dtl.DTLVardef@113dfd2_HPS_FORMAT_FIGEXP M_FIG C_FIG

ecology↗

bioRxiv2023

Contrasting Response of Microeukaryotic and Bacterial Communities to the Interplay of Seasonality and Stochastic Events in Shallow Soda Lakes

Seasonal environmental variation is a leading driver of microbial planktonic community assembly and interactions. Yet, unexpected departures from general seasonal successional trends are often reported. To understand the role of local stochastic events in modifying seasonal succession, we sampled fortnightly throughout three seasons (spring, summer, and autumn) five nearby shallow soda lakes exposed to the same seasonal meteorological changes. We characterised their microeukaryotic and bacterial communities by 18S and 16S rRNA gene sequencing, respectively. Biological interactions were inferred by the analyses of synchronous and time-shifted interaction networks, and the keystone taxa were topologically identified. The pans showed similar succession patterns during the study period with spring being characterised by high relevance of trophic interactions and certain level of community stability followed by a more dynamic and variable summer-autumn period both in respect of community composition and microbial interactions. Adaptation to general seasonal changes happened through the abundant shared core microbiome of the pans. However, stochastic events such as desiccation and cyanobacterial blooms disrupted common network attributes and introduced shifts from the prevalent seasonal trajectory. These were more pronounced for microeukaryotes than for bacteria which was reflected in increased turnover and contribution of non-core microeukaryotes. Our results demonstrated that despite being extreme and highly variable habitats, shallow soda lakes exhibit certain similarities in the seasonality of their planktonic communities, yet random stochastic events such as droughts can instigate substantial deviations from prevalent trends for the microeukaryotic but not bacterial communities.

microbiology↗

bioRxiv2021

Reconstruction and variability of tropical pollination networks in the Brazilian Atlantic Forest

O_LILoss of biodiversity comprehends not only the extinction of individual species, but also the loss of the ecological interactions among them. Survival of species, continuation of ecosystem functioning in nature, and ecosystem services to humans depend on the maintenance of well-functioning networks of species interactions (e.g. plant-pollinator networks and food webs). Analyses of ecological networks often rely on biased and incomplete survey data, especially in species-rich areas, such as the tropics. C_LIO_LIWe used a network inference method to reconstruct pollination data compiled from a large tropical rainforest habitat extent. To gain insight into the characteristics of plant-pollinator interactions across the region, we combined the reconstructed pollination network with species distribution modeling to obtain local pollination networks throughout the area. We explored how global network properties relate to natural forest cover and land cover heterogeneity. C_LIO_LIWe found that some network properties (the sum and evenness of link weights, connectance and nestedness) are positively correlated with forest cover, indicating that networks in sites with more natural habitat have greater diversity of interactions, stability and resilience. Modularity was not related to forest cover, but seemed to reflect habitat heterogeneity, due to the broad spatial scale of the study. C_LIO_LIWe believe that the methodology suggested here can facilitate the use of incomplete network data in a reliable way, and allow us to better understand and protect networks of species interactions in high biodiversity regions of the world. C_LI

ecology↗

bioRxiv2021

Food web aggregation: effects on key positions

Providing standard definitions of what should be considered as a node in food webs is still an unsolved problem. Especially for comparative and predictive food web modelling, a more systematic understanding is needed for the effects of trophic aggregation procedures. Aggregation is unavoidable during data management. Therefore, it is crucial to know whether food web properties are conserved during this process. Here, we study how different aggregation methods change the positional importance of species in food webs. In particular, we investigated the effects of various aggregation algorithms on 24 indices of importance. Our work was carried out on 76 aquatic food webs coming from the Ecopath with Ecosim database (EcoBase). We considered six main types of aggregation, according to the way that the nodes were clustered. These were (i) hierarchical clustering based on the Jaccard index, (ii) hierarchical clustering based on the regular equivalence index (REGE), (iii) maximisation of directed modularity, (iv) maximisation of modularity according to modules in which species fed on the same preys, (v) maximisation of modularity according to modules in which species are fed upon by the same predators, and (vi) clustering through the group model. Hierarchical clustering based on the Jaccard index and REGE index outperformed the other four methods on maintaining the relative importance of species for all the indices of importance (except for the contrastatus index (s') and betweenness centrality (BC)). The choice between these two methods should follow our research question and the importance index we are interested in studying. The other four aggregation methods change more the centrality of species, especially the one based on maximising directed modularity. When using these aggregation algorithms, one has to keep in mind that the network will not only be smaller but also provides different information.

ecology↗

bioRxiv2021

Understanding of the 2-oxoglutarate dehydrogenase and 2-oxoadipate dehydrogenase assembly with the E2o core relevant to a hybrid complex formation

The 2-oxoglutarate (OG) dehydrogenase complex (OGDHc) is a key enzyme in the tricarboxylic acid cycle (TCA) and comprises multiple copies of three components: 2-oxoglutarate dehydrogenase (hE1o), dihydrolipoamide succinyltransferase (hE2o), and dihydrolipoamide dehydrogenase (hE3). The OGDHc is one of the major regulators of mitochondrial metabolism through NADH and reactive oxygen species levels and impacts cell metabolic and cell signaling pathways through the coupling of OG metabolism to gene transcription, related to tumor cell proliferation and aging. The reduced OGDHc activity is linked to a number of neurodegenerative diseases. Evidence was obtained for the formation of a hybrid 2-oxo acid dehydrogenase complex between the OGDHc and its homologue 2-oxoadipate (OA) dehydrogenase (hE1a) in the L-lysine metabolic pathway, suggesting a potential cross-talk between the two distinct metabolic pathways. These findings raised fundamental questions about assembly of hE1a and hE1o to the hE2o core. Due to the lack of an atomic structure of the OGDHc from any sources, and of knowledge about exact distribution of components around the E2 core, hydrogen/deuterium exchange (HDX-MS) and chemical cross-linking mass spectrometry (CL-MS) have been carried out in binary hE1o-hE2o, hE1a-hE2o, hE1o-hE3 and hE2o-hE3 sub-complexes followed by structural modeling. Here we report findings that revealed some similarities in the assembly of hE1o and hE1a to the hE2o core. At the same time, three regions of the hE2o core comprising residues 191-208, 273-288, and 370-386 revealed a different binding mode to hE1o and hE1a, suggesting that hE2o can differentiate between these two proteins that may have physiological consequences.

biochemistry↗

bioRxiv2020

Inhibition and Crystal Structure of the Human DHTKD1-Thiamin Diphosphate Complex

DHTKD1 is the E1 component of the 2-oxoadipic acid dehydrogenase complex (OADHc), which functions in the L-lysine degradation pathway. Mutations in DHTKD1 have been associated with 2-aminoadipic and 2-oxoadipic aciduria, Charcot-Marie-Tooth disease type 2Q (CMT2Q) and eosinophilic esophagitis (EoE). A crystal structure and inhibitors of DHTKD1 could improve the understanding of these clinically distinct disorders, but are currently not available. Here we report the identification of adipoylphosphonic acid and tenatoprazole as DHTKD1 inhibitors using targeted and high throughput screening, respectively. We furthermore elucidate the DHTKD1 crystal structure with thiamin diphosphate bound at 2.1 [A]. The protein assembles as a dimer with residues from both monomers contributing to cofactor binding. We also report the impact of ten DHTKD1 missense mutations on the encoded proteins by enzyme kinetics, thermal stability and structural modeling. Some DHTKD1 variants displayed impaired folding (S777P and S862I), whereas other substitutions rendered the enzyme inactive (L234G, R715C and R455Q) or affected the thermal stability and catalytic efficiency (V360A and P773L). Three variants (R163Q, Q305H and G729R) surprisingly showed wild type like properties. Our work provides a structural basis for further understanding of the function of DHTKD1 and a starting point for selective small molecule inhibitors of the enzyme, which could help tease apart the role of this enzyme in several human pathologies.

biochemistry↗

bioRxiv2020

The OptoGenBox - a device for long-term optogenetics in C. elegans

Optogenetics controls neural activity and behavior in living organisms through genetically targetable actuators and light. This method has revolutionized biology and medicine as it allows controlling cells with high temporal and spatial precision. Optogenetics is typically applied only at short time scales, for instance to study specific behaviors. Optogenetically manipulating behavior also gives insights into physiology, as behavior controls systemic physiological processes. For example, arousal and sleep affect aging and health span. To study how behavior controls key physiological processes, behavioral manipulations need to occur at extended time scales. However, methods for long-term optogenetics are scarce and typically require expensive compound microscope setups. Optogenetic experiments can be conducted in many species. Small model animals such as the nematode C. elegans, have been instrumental in solving the mechanistic basis of medically important biological processes. We developed OptoGenBox, an affordable stand-alone and simple-to-use device for long-term optogenetic manipulation of C. elegans. OptoGenBox provides a controlled environment and is programmable to allow the execution of complex optogenetic manipulations over long experimental times of many days to weeks. To test our device, we investigated how optogenetically increased arousal and optogenetic sleep deprivation affect survival of arrested first larval stage C. elegans. We optogenetically activated the nociceptive ASH sensory neurons using ReaChR, thus triggering an escape response and increase in arousal. In addition, we optogenetically inhibited the sleep neuron RIS using ArchT, a condition known to impair sleep. Both optogenetic manipulations reduced survival. Thus, OptoGenBox presents an affordable system to study the long-term consequences of optogenetic manipulations of key biological processes in C. elegans and perhaps other small animals.

neuroscience↗

bioRxiv2019

Selection for altruistic defense in structured populations

We model natural selection for or against an anti-parasite (or anti-predator) defense allele in a host (or prey) population that is structured into many demes. The defense behavior has a fitness cost for the actor compared to non defenders ("cheaters") in the same deme and locally reduces parasite growth rates. Hutzenthaler et al. (2022) have analytically derived a criterion for fixation or extinction of defenders in the limit of large populations, many demes, weak selection and slow migration. Here, we use both individual-based and diffusion-based simulation approaches to analyze related models. We find that the criterion still leads to accurate predictions for settings with finitely many demes and with various migration patterns. A key mechanism of providing a benefit of the defense trait is genetic drift due to randomness of reproduction and death events leading to between-deme differences in defense allele frequencies and host population sizes. We discuss an inclusive-fitness interpretation of this mechanism and present in-silico evidence that under these conditions a defense trait can be altruistic and still spread in a structured population.

evolutionary biology↗