Biology subjects

Vandenabeele, P.

Publications and source records attributed to Vandenabeele, P..

7 recordsLinked to original sources

bioRxiv2026

Morphological and thermoregulatory responses to urbanization in the European garden spider Araneus diadematus.

Urbanization creates novel environments that can drive phenotypic and behavioural responses, yet how multiple traits respond across spatial scales remains poorly understood. In particular, elevated ambient temperatures via the urban heat island effect may drive morphological and behavioural responses. We investigated body size, abdominal colouration, microhabitat use, behavioural thermoregulation and thermal offset relative to ambient air in the orb-weaving spider Araneus diadematus across rural-urban gradients in northern Belgium. Contrary to predictions from the temperature-size rule, body size increased with urbanization at large spatial scales, whereas size-corrected abdomen area--reflecting body condition and reproductive investment--declined with urbanization, with strongest support at local spatial scales. Abdominal colouration showed no response to urbanization despite evidence for both carotenoid-like pigments and melanin-associated structures. Nevertheless, body size and colouration covaried, with sites containing larger spiders tending to harbour darker individuals, whereas within sites larger individuals were slightly brighter than smaller conspecifics. Thermal responses showed little variation along the urbanization gradient. Retreats were consistently warmer than web hubs, and spiders maintained body temperatures above both their immediate microhabitat and ambient air. Only retreat-associated behavioural thermoregulation showed a weak decline with urbanization at local spatial scales. Our results reveal contrasting trait responses to urbanization across spatial scales and demonstrate that size-colour covariation can persist despite divergent responses of individual traits. These findings highlight the importance of considering multiple traits, their covariation and spatial scale to accurately understand and predict ecological responses of ectotherms to urban environments.

ecology↗

bioRxiv2025

Zα domain-dependent ZBP1 condensate formation induces an amyloidal necroptotic signalling complex

ZBP1 restricts viral replication by inducing host cell death. ZBP1 recognises Z-RNA or Z-DNA, left-handed double-stranded RNA or DNA structures that accumulate after virus infection. How the interaction between Z-RNA/DNA and ZBP1 governs its activation and how this mediates downstream signalling remains unclear. Using herpes simplex virus 1 (HSV-1) as an activator of human ZBP1 we find that binding of the N-terminal Z domains of ZBP1 to Z-RNA induces ZBP1 condensate formation. This then mediates oligomerisation of the RIP homotypic interaction motifs (RHIMs) of ZBP1 establishing an amyloidal signalling complex with RIPK1 and RIPK3 that induces necroptotic cell death. We find that the kinase activity of RIPK1 is essential for RIPK1 and RIPK3 oligomerisation downstream of human ZBP1. Finally, the HSV-1-encoded RHIM-containing protein ICP6, does not interfere with Z domain-mediated ZBP1 condensate formation, but instead prevents downstream RIPK1 and RIPK3 oligomerisation thereby inhibiting necroptosis and promoting viral growth. Together, this shows that ZBP1 condensate formation restricts HSV-1 infection by promoting host cell necroptosis.

immunology↗

bioRxiv2025

Themis and Grb2 form a constitutive structural hub in T cell receptor signalling

Positive selection of thymocytes is essential for laying the foundations of the mammalian immune system that include the T cell repertoire, self-tolerance, and prevention of autoimmunity. Themis, the archetypal member of a metazoan protein family featuring distinctive CABIT domains, crucially regulates thymocyte positive selection by linking signalling by the T cell receptor (TCR) to the linker of activation of TCR (LAT). Intriguingly, Themis has been proposed to function via a constitutive complex with the multifunctional adaptor Grb2. Although poised to represent a paradigm shift in our understanding of TCR signalling, the structural and mechanistic basis of such an assembly has remained enigmatic. Here, we present the cryo-EM structure of Themis in complex with Grb2, which reveals how the tandem CABIT domains of Themis engulf the C-terminal SH3 domain of Grb2 (Grb2SH3C) to enable its latching onto the proline rich sequence of Themis. The remaining two domains of Grb2 adopt at least three conformational poses set to interact with other binding partners such as Sos1. Structural insights from unbound Themis unmask the pronounced flexibility of the CABIT domains of Themis, which becomes ordered upon binding to Grb2 to create a binding hotspot for their constitutive complex. Indeed, Themis variants that abrogate interactions with Grb2 also fail to activate the tyrosine phosphatase SHP-1 after TCR stimulation, analogous to the functional phenotype of Themis-deficient cells. Collectively, our study draws the blueprint of the Themis-Grb2 complex as a dynamic structural hub in T cell development.

immunology↗

bioRxiv2023

Type 1 immunity enables neonatal thymic ILC1 production

Thymic atrophy occurs following type 1 inflammatory conditions like viral infection and sepsis, resulting in cell death and disruption of T-cell development. However, it remains undetermined whether the thymus actively contributes to the immune response. Thus, we cultured neonatal thymus ex vivo with the type 1 cytokines IL-12 plus IL-18, resulting in a rapid shift from steady-state T-cell development to the production, expansion, and thymic exit of CXCR6+CD62L- type 1 innate lymphoid cells (ILC1s). Single-cell RNA-sequencing and functional assays identified these cells as embryonic-wave-derived KLRG1+ ILC1s that mainly differentiated from immature neonatal thymic ILC1s. Confocal 3D imaging confirmed neonatal thymic ILC1 expansion during MCMV infection. Furthermore, thymic grafts revealed in vivo thymic ILC1 egress and type 1 inflammation-induced homing of thymus-derived KLRG1+ ILC1s to the liver and peritoneal cavity. Altogether, our data reveal a novel thymic function where type 1 immunity enables the production and peripheral homing of thymic-derived ILC1s. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=185 SRC="FIGDIR/small/530451v1_ufig1.gif" ALT="Figure 1"> View larger version (56K): org.highwire.dtl.DTLVardef@d768corg.highwire.dtl.DTLVardef@1e20d77org.highwire.dtl.DTLVardef@1e206bforg.highwire.dtl.DTLVardef@292108_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2020

ADAR1 interaction with Z-RNA promotes editing of endogenous double-stranded RNA and prevents MDA5-dependent immune activation.

Loss-of-function of ADAR1 causes the severe autoinflammatory disease Aicardi-Goutieres Syndrome (AGS). ADAR1 converts adenosines into inosines within double-stranded (ds) RNA. This process called A-to-I editing masks self-dsRNA from detection by the antiviral dsRNA sensor MDA5. ADAR1 binds to dsRNA in both the canonical A-form and in the poorly defined Z-conformation (Z-RNA). Mutations in the Z-RNA binding Z-domain of ADAR1 are common in AGS patients. How loss of ADAR1/Z-RNA interaction contributes to disease development is unknown. Using ADAR1 Z-domain mutant human cells and knock-in mice, we demonstrate that abrogated binding of ADAR1 to Z-RNA leads to reduced A-to-I editing of dsRNA structures formed by pairing of inversely oriented SINEs. As a result, ADAR1 Z-domain mutant human cells and transgenic mice develop a spontaneous MDA5-dependent immune response. This shows that the interaction between ADAR1 and Z-RNA restricts sensing of self-dsRNA and prevents AGS development.

immunology↗

bioRxiv2020

Distinct EH domains of the endocytic TPLATE complex confer lipid and protein binding.

Clathrin-mediated endocytosis (CME) is the gatekeeper of the plasma membrane. In contrast to animals and yeasts, CME in plants depends on the TPLATE complex (TPC), an evolutionary ancient adaptor complex. The mechanistic contribution of the individual TPC subunits to plant CME remains however elusive. In this study, we used a multidisciplinary approach to elucidate the structural and functional roles of the evolutionary conserved N-terminal Eps15 homology (EH) domains of the TPC subunit AtEH1/Pan1. By integrating high-resolution structural information obtained by X-ray crystallography and NMR spectroscopy with all-atom molecular dynamics simulations, we provide structural insight into the function of both EH domains. Whereas one EH domain binds negatively charged PI(4,5)P2 lipids, unbiased peptidome profiling by mass-spectrometry revealed that the other EH domain interacts with the double N-terminal NPF motif of a novel TPC interactor, the integral membrane protein Secretory Carrier Membrane Protein 5 (SCAMP5). Furthermore, we show that AtEH/Pan1 proteins control the internalization of SCAMP5 via this double NPF peptide interaction motif. Collectively, our structural and functional studies reveal distinct but complementary roles of the EH domains of AtEH/Pan1 have in plant CME and connect the internalization of SCAMP5 to the TPLATE complex.

plant biology↗

bioRxiv2020

Sensing of endogenous nucleic acids by ZBP1 induces keratinocyte necroptosis and skin inflammation

Aberrant detection of endogenous nucleic acids by the immune system can cause inflammatory disease. The scaffold function of the signalling kinase RIPK1 limits spontaneous activation of the nucleic acid sensor ZBP1. Consequently, loss of RIPK1 in keratinocytes induces ZBP1-dependent necroptosis and skin inflammation. Whether nucleic acid sensing is required to activate ZBP1 in RIPK1 deficient conditions and which immune pathways are associated with skin disease remained open questions. Using knock-in mice with disrupted ZBP1 nucleic acid binding activity, we report that sensing of endogenous nucleic acids by ZBP1 is critical in driving skin pathology characterised by antiviral and IL-17 immune responses. Inducing ZBP1 expression by interferons triggers necroptosis in RIPK1-deficient keratinocytes and epidermis-specific deletion of MLKL prevents disease, demonstrating that cell-intrinsic events cause inflammation. These findings indicate that dysregulated sensing of endogenous nucleic acid by ZBP1 can drive inflammation and may contribute to the pathogenesis of IL-17-driven inflammatory skin conditions such as psoriasis. SummaryDevos, Tanghe et al. find that the recognition of endogenous nucleic acids by the nucleic acid sensor ZBP1 causes necroptosis of RIPK1-deficient keratinocytes. This process drives the development of an inflammatory skin disease characterised by an IL-17 immune response.

immunology↗