Biology subjects

Schmitt, L.

Publications and source records attributed to Schmitt, L..

At least 19 recordsLinked to original sources

bioRxiv2026

The multidrug transporter Pdr5 from Saccharomyces cerevisiae is an ergosterol-modulated efflux pump

The pleiotropic drug resistance ABC transporter Pdr5 and its homologs play a critical role in multidrug resistance of numerous fungi, including pathogens. Previous studies demonstrated that alterations in the composition of the plasma membrane in which Pdr5 is embedded, specifically the ergosterol content, affected transport activity. Here we report the cryo-EM map of Saccharomyces cerevisiae Pdr5 in complex with ATP/ADP at 2.2 [A] resolution, revealing densities on the surface of the transmembrane domains as well as inside the substrate-binding site, that were assigned as ergosterol, identified and quantified by GC-MS, and the sphingolipid M(IP)2C, identified via native MS. The ergosterol molecules are bound to the protein in well-defined grooves and unexpected locations. We found that the activity of Pdr5 follows a Gaussian-like distribution, increasing with the ergosterol-concentration to reach a maximum before declining at higher concentrations, but this modulation was not observed in the presence of cholesterol, the sterol analogue found in mammalian cells. Mutational analysis corroborates the role of a single ergosterol-binding site in the modulation of Pdr5 activity. Our structural analysis identifies a protein-lipid network that could serve as a center for lipid engagement linking the surrounding lipid environment to the substrate-binding region of Pdr5. These findings advance our understanding of Pdr5 function by demonstrating that the lipid environment is closely linked to Pdr5 structure and activity.

biochemistry↗

bioRxiv2026

Spatial landscape of pretransplant liver disease and post-transplant immune outcomes in children

Defining molecular patterns underlying pediatric end-stage liver disease and its treatment with liver transplantation requires rich datasets spanning a multitude of diagnoses and transplant outcomes. Here, we describe the spatial molecular landscape of approximately five million liver cell profiles from 98 liver tissue samples. The samples span donor liver, used here as a reference tissue, and end-stage diseases including biliary atresia, progressive familial intrahepatic cholestasis, hepatoblastoma, acute liver failure, and gestational alloimmune liver disease. Post-transplant liver allograft biopsies include those without and with T-cell-mediated and antibody-mediated rejection, mixed pathology, and outcome groups from immunosuppression withdrawal studies. Samples were profiled using the CosMx Human Universal Cell Characterization RNA Panel (1K) and the CosMx Human 6K Discovery Panel (6K). Preliminary exploratory analyses include cellular composition and gene abundance and variability across clinical cohorts. A twelve-gene signature comprising the genes with the highest variance implicates acute-phase response genes (e.g., SAA1) and profibrotic genes (e.g., COL1A1) as a shared link across these otherwise distinct conditions. This injury-repair-remodeling gene network warrants further investigation through higher-resolution, zone-specific spatial mapping to help clarify disease pathogenesis.

genomics↗

bioRxiv2026

Ubp3 mediates dynamic deubiquitination of mitochondria upon induction of mitophagy

Ensuring quality and maintenance of mitochondria within eukaryotic cells is important for cellular fitness. One critical pathway that needs to be tightly controlled to achieve this is mitophagy, which is negatively regulated by the deubiquitinase Ubp3 in Saccharomyces cerevisiae. Here we show that beyond this established role of Ubp3, it is critical to mediate substantial temporal changes of the mitochondrial ubiquitin landscape during mitophagy. Isolated mitochondria displayed extensive ubiquitination under steady-state conditions, whereas rapamycin-mediated induction of mitophagy/autophagy led to a progressive elimination of mitochondrial ubiquitination. A systematic screening analysis revealed that Ubp3 and Ubp4 are crucial regulators of rapamycin-induced mitochondrial deubiquitination. Deletion of Bre5, a cofactor of Ubp3, or of the UBI4 gene, encoding Ubi4 required for mitophagy, did not impair deubiquitination of mitochondria during mitophagy, indicating that Ubp3 has additional functions. We further showed that Ubi4 acts epistatic to Ubp3 for regulating mitophagy, supporting that mitophagy does not simply depend on the extent of mitochondrial ubiquitination, but rather on specific ubiquitinated substrates. Consistent with the role of Ubp3 in vivo, purified Ubp3 or its catalytic domain alone were sufficient to efficiently deubiquitinate isolated mitochondria in vitro in a Bre5-independent manner. Together, these findings highlight Ubp3 as a prominent rheostat of mitochondrial ubiquitin remodelling, revealing mitochondrial ubiquitin storage and its dynamic release as another layer of stress regulation by ubiquitin-dependent quality control pathways.

cell biology↗

bioRxiv2026

The Type VI secretion effector TpeX expands the pore-forming virulence arsenal of Pseudomonas aeruginosa

The type VI secretion system (T6SS) is a major weapon used by Pseudomonas aeruginosa to antagonize competing bacteria through the delivery of a diverse repertoire of toxic effectors. Although several P. aeruginosa T6SS effectors target bacterial membranes, the mechanisms underlying membrane disruption remain poorly characterized. Here, we study TpeX (PA5265), an accessory T6SS effector from P. aeruginosa PAO1 with structural similarity to the VasX pore-forming effector of Vibrio cholerae. We show that membrane-targeted TpeX exerts a bactericidal activity in Escherichia coli, resulting in dissipation of the membrane potential and loss of membrane integrity. The TpeX C-terminal region containing the predicted colicin-like transmembrane domain is sufficient to confer toxicity, although with reduced activity, supporting its role as the membrane-disrupting module. TpeX also oligomerizes upon membrane targeting, forming at least dimers, and structural modelling predicts a membrane-embedded pore compatible with the observed permeabilization phenotype. We further identify TpiX (PA5264), the protein encoded by the downstream gene, as the cognate immunity protein, which partially protects cells from TpeX toxicity and interacts with TpeX. Finally, AlphaFold 3 modelling predicts an interaction between TpeX and the HcpB-VgrG6 T6SS spike, suggesting a possible mechanism for effector recruitment and delivery. Together, our results identify TpeX as a bactericidal, colicin-like pore-forming T6SS effector whose membrane activity is controlled by a cognate immunity protein, thereby expanding the repertoire of membrane-targeting weapons used by P. aeruginosa in interbacterial competition.

microbiology↗

bioRxiv2026

In vitro characterization of the baker's yeast deubiquitinase Ubp3

Ubp3 is one of about 20 deubiquitinases (DUBs) in S. cerevisiae. The current view generally assumes that Ubp3 requires its interaction partner Bre5, which is proposed to function as a positive regulator. Accordingly, the Ubp3/Bre5 complex has been implicated in a broad range of cellular processes for example trafficking between ER and Golgi, stress granule formation and selective autophagy. However, the molecular basis of this proposed Bre5-dependent activity remains unclear. To address this at a molecular level, Ubp3, Bre5, and related constructs were heterologously expressed in E. coli, purified to homogeneity, and characterized in vitro. Both proteins contain folded domains as well as extensive intrinsically disordered regions (IDRs). Despite this structural complexity, the Ubp3/Bre5 complex could be isolated following either co-expression in vivo or after in vitro assembly. Unexpectedly, complex formation with Bre5 was not required for the catalytic activity of full length Ubp3. Furthermore, even the isolated catalytic domain of Ubp3 was fully active against two distinct substrates in the absence of Bre5, demonstrating that its deubiquitinating activity is intrinsically independent of Bre5. These findings indicate that the catalytic domain alone is sufficient for substrate cleavage, whereas the extensive IDRs of Ubp3 and its cofactor Bre5 might contribute to substrate recognition or specificity. Overall, this study challenges the prevailing model of Bre5-dependent activation of Ubp3 and provides new insights into the molecular organization of the Ubp3/Bre5 system. More broadly, it highlights the importance of intrinsically disordered regions in regulating deubiquitinase function and cellular signaling networks.

biochemistry↗

bioRxiv2026

Molecular basis of Gram-positive host recognition by the Oenococcus oeni phage OE33PA

Bacteriophages (phages) infecting Gram-positive bacteria must bind to host receptors across thick cell walls to initiate infection, yet the underlying structural mechanisms remain unclear. Here, we report cryo-electron microscopy structures of the Oenococcus oeni siphophage OE33PA, providing the first atomic resolution view of a phage infecting this bacterium important for the wine industry. While the overall virion architecture is conserved, the adhesion device displays distinctive features. Its receptor-binding proteins adopt multiple orientations, revealing an intrinsically dynamic assembly. In situ cryo-electron tomography captures distinct conformations upon host attachment, providing rare structural insight into interactions with Gram-positive hosts. Additionally, functional assays show that a highly mobile carbohydrate-binding module in the distal tail protein mediates host-specific binding. Furthermore, the tape measure protein, central to phage assembly and infectivity, adopts a hexameric organization, updating the prevailing trimeric model in siphophages. Together, these findings reveal a dynamic adhesion device in a phage infecting Gram-positive bacteria and highlight the structural and functional diversity of phages.

microbiology↗

bioRxiv2026

Drosophila Arc1 is required for metabolic resilience and developmental timing during dietary challenges

Energy homeostasis at the organismal level requires balancing energy storage and mobilization to provide sufficient fuel for energy-intensive processes like development without depleting or accumulating excess stores. Fluctuations in the nutritional content of the diet present a challenge to the pathways that maintain energy balance. We previously identified the Drosophila melanogaster counterpart of human ARC (activity-regulated cytoskeleton-associated protein) as a brain-expressed protein that regulates energy storage in the major fat storage tissue of the fly, the fat body. Here we show that Arc1 expression in the brain responds to changes in diet and insulin-like peptide levels. Mutating Arc1 perturbs the ability of larvae to maintain normal body fat and rates of development upon dietary changes: mutants develop slower or faster than wild-type on nutrient-poor or nutrient-rich diets, respectively. Excess fat storage in Arc1 mutants becomes an advantage upon starvation, prolonging survival relative to the wild type. In addition to metabolic and neuronal genes, transcriptomic analysis revealed changes in key developmental drivers of development, in both diet-dependent and - independent manners. This study supports a model in which nutrient regulation of Arc1 via insulin-like peptide signaling couples dietary changes to changes in metabolism -- to maintain energy homeostasis -- and production of hormone signals, to support timely development. In this role, Arc1 is a central player in a buffering mechanism that coordinates nutrient availability, organismal metabolism, and developmental rate.

genetics↗

bioRxiv2025

Membrane Transport of Rhodamine 6G by the reconstituted multidrug resistance ABC transporter Pdr5 in Horizontal Lipid Bilayer

Pdr5 is the most abundant ABC transporter in Saccharomyces cerevisiae and plays a key role in the pleiotropic drug resistance (PDR) network, actively preventing the sustained entry of a wide range of structurally diverse compounds into the cell. This transporter has been extensively studied in vivo, in plasma membrane vesicles, and more recently, after reconstitution into artificial membranes, making it a widely used model system for ABC transporter research. Recent structural studies of Pdr5 have provided new insights into its architecture and function. However, the precise molecular mechanisms underlying Pdr5-mediated membrane transport remain largely unresolved. In this study, we investigate the interaction of reconstituted Pdr5 in an artificial freestanding horizontal lipid bilayer system with Rhodamine 6G (R6G), a well-known Pdr5 substrate. We show that functionally reconstituted Pdr5 actively transports the R6G+ cation across the membrane in an ATP-dependent manner, moving it from one bulk phase to the other.

biophysics↗

bioRxiv2025

Molecular Insights into CLD Domain Dynamics and Toxin Recruitment of the HlyA E. coli T1SS

Escherichia coli is a Gram-negative opportunistic pathogen causing nosocomial infections through the production of various virulence factors. Type 1 secretion systems (T1SS) contribute to virulence by mediating one-step secretion of unfolded substrates directly into the extracellular space, bypassing the periplasm. A well-studied example is the hemolysin A (HlyA) system, which secretes the HlyA toxin in an unfolded state across the inner and outer membranes. T1SS typically comprise a homodimeric ABC transporter (HlyB), a membrane fusion protein (HlyD), and the outer membrane protein TolC. Some ABC transporters in T1SS also contain N-terminal C39 peptidase or peptidase-like (CLD) domains implicated in substrate interaction. Recent cryo-EM studies have resolved the inner-membrane complex as a trimer of HlyB homodimers with associated HlyD protomers. However, a full structural model including TolC remains unavailable. We present the first complete structural model of the HlyA T1SS, constructed using template- and MSA-based information and validated by SAXS. Molecular dynamics simulations provide insights into the function of the CLD domains, which are partially absent from existing cryo-EM structures. These domains may modulate transport by stabilizing specific conformations of the complex. Simulations with a C-terminal fragment of HlyA indicate that toxin binding occurs in the occluded conformation of HlyB, potentially initiating substrate transport through a single HlyB protomer before transitioning to an inward-facing state. HlyA binding also induces allosteric effects on HlyD, altering key residues involved in TolC recruitment. These results indicate how substrate recognition and transport are coupled and may support the development of antimicrobial strategies targeting the T1SS.

biophysics↗

bioRxiv2025

Event-Related Spatio-Spectral Perturbation (ERSSP): A Scalp-Wide EEG Analysis Framework for Capturing Extralemniscal Thalamocortical Activity, Validated Using a Fragile X Syndrome Model

The extralemniscal thalamocortical pathway regulates large-scale modulation of cortical states but remains inaccessible to traditional EEG analysis due to its diffuse, variable, and asynchronous nature. To address this, we introduce the Event-Related Spatio-Spectral Perturbation (ERSSP) framework, which quantifies spatially distributed time-frequency responses. ERSSP summarizes the number of channels exhibiting significant spectral perturbations, capturing diffuse cortical dynamics from sensor-space EEG. We validated this approach using a passive auditory habituation task in individuals with Fragile X Syndrome (FXS), a condition marked by disrupted thalamocortical modulation. ERSSP revealed enhanced spatial extent of power increases (but not phase-locking) in FXS compared to controls. Results also showed expected gender differences, further supporting biological sensitivity of ERSSP. ERSSP provides a conceptually simple and computationally efficient method for quantifying broadly distributed sensory modulation and may enable new insights into thalamocortical function in both basic and clinical neuroscience.

neuroscience↗

bioRxiv2025

Acylation of the RTX Toxin MbxA stimulates host membrane disruption through a specific interaction with cholesterol

RTX toxins, characterized by their calcium-binding glycine-rich repeat regions, are known for their ability to disrupt host cell membranes. Although the acylation of specific lysine residues in these toxins is established as crucial for their hemolytic activity, the precise mechanisms underlying this enhancement remain unclear. In this study, we explore the role of acylation in the pore-forming behaviour of the RTX toxin MbxA by comparing the lytic activities of acylated MbxA and its non-acylated form, proMbxA, on in vitro membrane systems, as well as living cells. Our findings demonstrate that a cholesterol specific interaction promotes MbxA- induced membrane disruption in an acylation-dependent manner. Further analysis revealed that acylation is not necessary for initial membrane binding but markedly enhances pore formation. Overall, our results offer valuable insights into the molecular determinants that regulate RTX toxin activity, highlighting a complex interplay between lipid composition (sterols), acylation, and membrane disruption, thereby advancing our understanding of RTX toxin pathogenesis.

biochemistry↗

bioRxiv2025

Liver transplant rejection features memory cell priming, spatially differentiated networks and novel drug targets.

Acute T-cell-mediated transplant rejection, the earliest contributor to immunological graft failure responds variably to T-cell suppression. Early rejection can co-exist with donor-specific antibodies which also shorten graft survival, without affecting graft histology visibly. Here, during early liver transplant rejection, blood leukocytes manifest primed T-cells with heat shock protein (HSP) signaling and transcriptional programs for memory cell expansion. Corresponding biopsies demonstrate upregulated immune synapse and proteasomal genes in T-cell-infiltrated portal and central regions of the liver lobule. With donor-specific antibodies, the intervening intralobular region demonstrates a germinal-center-like allograft response with upregulated CD40, chemokine, T-follicular and complement signaling, which intensifies along the direction of sinusoidal blood flow from portal to central regions. Proteasomal and HSP90 inhibitors suppress donor-specific alloresponses of T- and B-cells in blood samples from patients with early rejection. The molecular injury spectrum of early rejection is complex, spatially differentiated and reveals novel early immunosuppressive strategies to extend graft survival.

immunology↗

bioRxiv2024

Novel interactions within the silent information regulator heterochromatin complex potentiate inter-subunit communication and gene repression

Organisms with smaller genomes often perform multiple functions using one multi-subunit protein complex. The S. cerevisiae Silent Information Regulator complex (SIRc) carries out all of the core functions of heterochromatin. SIR complexes first drive the initiation and spreading of histone deacetylation in an iterative manner. Subsequently, the same complexes are incorporated stably with nucleosomes, driving compaction and repression of the underlying chromatin domain. These two distinct functions of SIRc have each been characterized in much detail, but the mechanism by which the dynamic spreading state switches to stable compaction is not well-understood. This incomplete knowledge of potential intra-complex communication is partly due to a lack of structural information of the complex as a whole; only structures of fragments have been determined to date. Using cross-linking mass spectrometry in solution, we identified a novel inter-subunit interaction that physically connects the two states of SIRc. The Sir2 deacetylase makes direct interactions with the scaffolding subunit Sir4 through its coiled-coil domain, which also interacts with the Sir3 compaction/repression subunit. Within the hub of interactions are conserved residues in Sir2 that can sense deacetylation state, as well as amino acids that likely diverged and co-evolved to interact with Sir4, promoting species-specific functions. Mutation of this interaction hub disrupts heterochromatic repression, potentially by disrupting a conserved mechanism that communicates completion of deacetylation to switch to compaction. Our work highlights how a single multi-functional chromatin regulatory complex can stage a step-wise mechanism that requires a major transition in activities to achieve epigenetic gene repression.

molecular biology↗

bioRxiv2024

m6A-mediated epi-transcriptomic dysregulation underlies synaptic dysfunction in fragile X syndrome

Fragile X syndrome (FXS), the leading genetic cause of intellectual disability, arises from FMR1 gene silencing and loss of the FMRP protein. N6-methyladenosine (m6A) is a prevalent mRNA modification essential for post-transcriptional regulation. FMRP is known to bind to and regulate the stability of m6A-containing transcripts. However, how loss of FMRP impacts on transcriptome-wide m6A modifications in FXS patients remains unknown. To answer this question, we generated cortical neurons differentiated from induced pluripotent stem cells (iPSC) derived from healthy subjects and FXS patients. In electrophysiology recordings, we validated that synaptic and neuronal network defects in iPSC-derived FXS neurons corresponded to the clinical EEG data of the patients from which the corresponding iPSC line was derived. In analysis of transcriptome-wide methylation, we show that FMRP deficiency led to increased translation of m6A writers, resulting in hypermethylation that primarily affecting synapse-associated transcripts and increased mRNA decay. Conversely, in the presence of an m6A writer inhibitor, synaptic defects in FXS neurons were rescued. Taken together, our findings uncover that an FMRP-dependent epi-transcriptomic mechanism contributes to FXS pathogenesis by disrupting m6A modifications in FXS, suggesting a promising avenue for m6A- targeted therapies.

neuroscience↗

bioRxiv2024

Frontal Cortex Hyperactivation and Gamma Desynchrony in Fragile X Syndrome: Correlates of Auditory Hypersensitivity

Fragile X syndrome (FXS) is an X-linked disorder that often leads to intellectual disability, anxiety, and sensory hypersensitivity. While sound sensitivity (hyperacusis) is a distressing symptom in FXS, its neural basis is not well understood. It is postulated that hyperacusis may stem from temporal lobe hyperexcitability or dysregulation in top-down modulation. Studying the neural mechanisms underlying sound sensitivity in FXS using scalp electroencephalography (EEG) is challenging because the temporal and frontal regions have overlapping neural projections that are difficult to differentiate. To overcome this challenge, we conducted EEG source analysis on a group of 36 individuals with FXS and 39 matched healthy controls. Our goal was to characterize the spatial and temporal properties of the response to an auditory chirp stimulus. Our results showed that males with FXS exhibit excessive activation in the frontal cortex in response to the stimulus onset, which may reflect changes in top-down modulation of auditory processing. Additionally, during the chirp stimulus, individuals with FXS demonstrated a reduction in typical gamma phase synchrony, along with an increase in asynchronous gamma power, across multiple regions, most strongly in temporal cortex. Consistent with these findings, we observed a decrease in the signal-to-noise ratio, estimated by the ratio of synchronous to asynchronous gamma activity, in individuals with FXS. Furthermore, this ratio was highly correlated with performance in an auditory attention task. Compared to controls, males with FXS demonstrated elevated bidirectional frontotemporal information flow at chirp onset. The evidence indicates that both temporal lobe hyperexcitability and disruptions in top-down regulation play a role in auditory sensitivity disturbances in FXS. These findings have the potential to guide the development of therapeutic targets and back-translation strategies.

neuroscience↗

bioRxiv2024

The Role of the Co-Chaperone DNAJB11 in Polycystic Kidney Disease: Molecular Mechanisms and Cellular Origin of Cyst Formation

Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in PKD1 and PKD2, encoding polycystin-1 (PC1) and polycystin-2 (PC2), which are required for the regulation of the renal tubular diameter. Loss of polycystin function results in cyst formation. Atypical forms of ADPKD are caused by mutations in genes encoding endoplasmic reticulum (ER)-resident proteins through mechanisms that are not well understood. Here, we investigate the function of DNAJB11, an ER co-chaperone associated with atypical ADPKD. We generated mouse models with constitutive and conditional Dnajb11 inactivation and Dnajb11-deficient renal epithelial cells to investigate the mechanism underlying autosomal dominant inheritance, the specific cell types driving cyst formation, and molecular mechanisms underlying DNAJB11-dependent polycystic kidney disease. We show that biallelic loss of Dnajb11 causes cystic kidney disease and fibrosis, mirroring human disease characteristics. In contrast to classical ADPKD, cysts predominantly originate from proximal tubules. Cyst formation begins in utero and the timing of Dnajb11 inactivation strongly influences disease severity. Furthermore, we identify impaired PC1 cleavage as a potential mechanism underlying DNAJB11-dependent cyst formation. Proteomic analysis of Dnajb11- and Pkd1-deficient cells reveals common and distinct pathways and dysregulated proteins, providing a foundation to better understand phenotypic differences between different forms of ADPKD.

molecular biology↗

bioRxiv2024

Somatic gene delivery for flexible in vivo modeling of high-risk sarcoma

A particular challenge hampering therapeutic advancements for high-risk sarcoma patients is the broad spectrum of molecularly distinct sarcoma entities and the corresponding lack of suitable model systems to recapitulate and study these diseases. To overcome this predicament, we developed a novel genetically-controlled, yet versatile mouse modeling platform allowing delivery of different genetic lesions by electroporation (EPO) of the thigh muscle wildtype mice. This optimized sarcoma EPO-GEMM (EPO-based genetically engineered mouse model) platform allowed the generation of ten biologically distinct sarcoma entities, including Synovial Sarcoma (SS), fusion-positive and fusion-negative Rhabdomyosarcoma (RMS), Alveolar Soft Part Sarcoma (ASPS), Undifferentiated Pleomorphic Sarcoma (UPS) and Infantile Fibrosarcoma (IFS). Comprehensive molecular profiling and cross-species analyses confirmed faithful recapitulation of the human disease, including the expression of relevant immunotherapy targets. Syngeneic allografting enabled reliable preservation and scalability of Sarcoma-EPO-GEMMs for treatment trials, such as B7-H3-directed CAR-T cell therapy in an immunocompetent background.

cancer biology↗

bioRxiv2023

Above- and below-ground links mediated by arboreal ants and host tree modify soil aggregation scaling, infiltration, and chemistry

Soils are increasingly recognized as complex systems, emphasizing a need to study unique properties such as long-tailed scaling laws and the role of indirect interactions among arboreal above- and below-ground soil invertebrates. However, few studies consider the above-below-ground connections mediated by invertebrates activity and behavior compared to mediated by tree physiology. Given previous work showing that arboreal ants can compete and affect ground foragers as well as alter foraging behavior on different host trees, it is plausible that persistent above-ground ant nesting could extend to affect soil properties including structure and chemistry, mediated by ground ant exclusion. This study analyzes soil aggregation, water infiltration, and macro-chemical data associated with longer-term (5+ year) ant nesting in a rustic tropical agroforest. Results show that, 1) ant nesting maintained scaling law exponents or fractal dimensions of soil aggregate size distributions, and was significantly associated with relatively larger micro-aggregate diameters and log-normal variance in macro-aggregate size distributions, suggesting more consistent (less variable) underlying aggregation processes similar to host tree species effects; 2) areas in the vicinity of trees with no dominant ant nests had three-times faster water infiltration than in the vicinity of trees with dominant ant nests; and 3) a tendency toward changes in soil carbon and nitrogen stocks by one-quarter depending on host tree. These patterns are consistent with expected effects of ground ant suppression by an aggressive keystone arboreal ant, and are supported by previous studies reporting positive ground ant nest effects on soil chemistry and documenting ground ant foraging as a source of soil aggregate fragmentation. This study presents new ecological processes affecting ecosystem-scale functions, and suggests that future research on indirect interaction cascades would be beneficial to advance fundamental understanding of whole-ecosystem processes.

ecology↗