Biology subjects

Heyman, J.

Publications and source records attributed to Heyman, J..

5 recordsLinked to original sources

bioRxiv2025

The coronavirus envelope is conserved, contains bioactive lipids needed for replication, and is modulated in response to host inflammation

How inflammation or disease regulates coronavirus lipid membranes is currently unknown, while patient-derived viral envelopes have never been structurally characterized. Here, we show that four cultured SARS-CoV-2 strains (England2, Alpha, Beta, and Delta) possess conserved, phospholipid- and cholesterol-rich envelopes, with pro-thrombotic and infection-promoting aminophospholipids (aPL) displayed predominantly on the outer leaflet (approximately 70-80%). Exposure to interleukin-4 (IL-4) markedly altered envelope fatty acyl composition, whereas interleukin-6 (with or without its soluble receptor IL-6R) and dexamethasone had no detectable effect. Viral envelopes were susceptible to hydrolysis by secretory phospholipase A2 (sPLA2), an enzyme associated with adverse clinical outcomes. SARS-CoV-2 isolated directly from patient saliva exhibited cholesterol-enriched envelopes that were highly conserved across clinical isolates. In addition, clinical samples contained pro-coagulant oxidized phospholipids and bioactive lipoxygenase (LOX)-derived oxylipins. The dominance of external facing pro-coagulant aPL and eoxPL may support known thrombotic complications of severe COVID19 viremia. Last, gene-silencing experiments demonstrated that 15-LOX2 is required for replication of related coronaviruses. Together, these findings reposition the coronavirus envelope as an active, dynamic structure rather than a passive scaffold, and challenge the protein-centric view of viral function. The lipid envelope is proposed as a potential therapeutic target through modulation of host innate immunity, and dampening thrombotic potential. Significance statementViruses such as SARS-CoV-2 are surrounded by a host-derived lipid envelope. Little is known about how this changes during infection/inflammation. We determined the lipid composition of the SARS-CoV-2 envelope using both laboratory-grown viruses and patient isolates. Across several pandemic strains, the envelope was rich in cholesterol and phospholipids and showed a consistent structure. Lipids linked to thrombosis and infection were mainly exposed on the outer virus surface. The inflammatory cytokine interleukin-4 altered the envelopes fatty acid composition, while other treatments did not. Patient-derived viruses contained additional bioactive lipids, and blocking an enzyme that generates these lipids reduced coronavirus replication. In summary, the envelope is an active component of infection and potential target for new treatments to dampen infectivity and thrombosis.

immunology↗

bioRxiv2024

SIM and CCS52A1 control root hair cell endoreplication and expansion

Arabidopsis thaliana (Arabidopsis) root hair cells undergo rapid cell elongation that is correlated with an increased DNA ploidy level through endoreplication. However, the contribution of endoreplication to hair cell growth is currently unclear. Here, we determined ploidy levels within the root hair cell file from the proximal meristem to the elongation zone and correlated them with cellular parameters. Our data show that cells in the basal meristem reach a 4C level prior to rapid elongation, whereas in the elongation zone a 16C level is reached prior to the onset of tip growth, suggesting that endoreplication is a prerequisite for rapid volume increase. Consistently, we show that mutants in SIAMESE (SIM) and CELL CYCLE SWITCH52 A1 (CCS52A1), key endocycle regulators expressed in hair cells, display a decrease in cell volume and hair tip length. Interestingly, SIM and CCS52A1 affect cell width and length, respectively. In addition, CCS52A1 controls the growth rate of the root hair tip. Given the common association between cell expansion and cell wall modifications, we performed immunolabeling on wild-type and mutant roots, which revealed a reduced level of pectin methylesterification in the mutant backgrounds, suggesting that SIM and CCS52A1 may modulate root hair cell growth by affecting cell wall modifications. The author responsible for distribution of materials integral to the findings presented in this article in accordance with the policy described in the Instructions for Authors (https://academic.oup.com/plphys/pages/General-Instructions) is Lieven De Veylder (lieven.deveylder@psb.vib-ugent.be). ONE-SENTENCE SUMMARYSIM and CCS52A1 control Arabidopsis root hair cell volume by controlling endoreplication.

plant biology↗

bioRxiv2021

The regeneration factors ERF114 and ERF115 act as transducers of mechanical cues to developmental pathways

Plants show an unparalleled regenerative capacity, allowing them to survive severe stress conditions, such as injury, herbivory attack and harsh weather conditions. This potential not only replenishes tissues and restores damaged organs, but can also give rise to whole plant bodies, highlighting the intertwined nature of development and regeneration. It suggests that regeneration and developmental processes respond to the same upstream signals, but how a cell knows which of the two processes to engage is currently unknown. Here, we demonstrate that next to being regulators of regeneration, ETHYENE RESPONSE FACTOR 114 (ERF114) and ERF115 govern developmental growth in the absence of wounding or injury. Increased ERF114 and ERF115 activity is correlated with enhanced xylem maturation and lateral root formation, whereas their knockout results in a decrease in lateral roots and xylem connectivity following grafting. Moreover, we provide evidence that mechanical cues contribute to ERF114 and ERF115 expression in correlation with BZR1 mediated brassinosteroid signaling under both regenerative and developmental conditions. Antagonistically, negative regulation of cell wall extensibility via cell wall-associated mechanosensory FERONIA signaling suppresses their expression under both conditions. Our data suggest a molecular framework in which mechanical perturbations too great to be compensated by adaptive cell wall remodeling results in strong ERF114 and ERF115 expression, switching their role from developmental to regenerative regulators. One-Sentence SummaryMechanical cues drive ERF114/ERF115 expression during lateral root development as well as regeneration.

plant biology↗

bioRxiv2021

The APC/CCCS52A2 E3-Ligase Complex targeted PKN1 Protein is a Plant Lineage-Specific Driver of Cell Division

The anaphase-promoting complex/cyclosome (APC/C) marks key cell cycle proteins for proteasomal breakdown, thereby ensuring unidirectional progression through the cell cycle. Its target recognition is temporally regulated by activating subunits, one of which is called CELL CYCLE SWITCH 52 A2 (CCS52A2). We sought to expand the knowledge of identified APC/C targets by using the severe growth phenotypes of CCS52A2-deficient Arabidopsis thaliana plants as a readout in a suppressor mutagenesis screen, resulting in the identification of the previously undescribed gene called PIKMIN1 (PKN1). PKN1 deficiency rescues the disorganized root stem cell phenotype of the ccs52a2-1 mutant, whereas an excess of PKN1 inhibits growth of ccs52a2-1 plants, indicating the importance of PKN1 abundance for proper development. Accordingly, the lack of PKN1 in a wild-type background negatively impacts cell division, while its ectopic expression promotes proliferation. PKN1 shows a cell cycle phase-dependent accumulation pattern, localizing to microtubular structures, including the preprophase band, the mitotic spindle, and phragmoplast. PKN1 is conserved throughout the plant kingdom, with its function in cell division being evolutionary conserved in the liverwort Marchantia polymorpha. Our data thus demonstrate that PKN1 represents a novel, plant-specific gene with a rate-limiting role in cell division, which is proteolytically controlled by the CCS52A2-activated APC/C. One-Sentence SummaryPKN1 is a conserved plant-specific protein that is rate-limiting for cell division, likely through its interaction with microtubuli, and is proteolytically controlled by APC/CCCS52A2.

plant biology↗

bioRxiv2020

CYCA3;4 Is a Post-Prophase Target of the APC/CCCS52A2 E3 Ligase Controlling Formative Cell Divisions in Arabidopsis

The Anaphase Promoting Complex/Cyclosome (APC/C) controls unidirectional progression through the cell cycle by marking key cell cycle proteins for proteasomal turnover. Its activity is temporally regulated by the docking of different activating subunits, known in plants as CDC20 and CCS52. Despite the importance of the APC/C during cell proliferation, the number of identified targets in the plant cell cycle is limited. Here, we used the growth and meristem phenotypes of Arabidopsis CCS52A2-deficient plants in a suppressor mutagenesis screen to identify APC/CCCS52A2 substrates or regulators, resulting in the identification of a mutant cyclin CYCA3;4 allele. CYCA3;4 deficiency partially rescues the early ccs52a2-1 phenotypes, whereas increased CYCA3;4 levels enhances them. Furthermore, whereas CYCA3;4 proteins are promptly broken down after prophase in wild-type plants, they remain present in later stages of mitosis in ccs52a2-1 mutant plants, marking them as APC/CCCS52A2 substrates. Strikingly, CYCA3;4 overexpression results in aberrant root meristem and stomatal divisions, mimicking phenotypes of plants with reduced RBR1 activity. Correspondingly, RBR1 hyperphosphorylation was observed in CYCA3;4-overproducing plants. Our data thus demonstrate that an inability to timely destroy CYCA3;4 attributes to disorganized formative divisions, likely in part caused by the inactivation of RBR1. ONE-SENTENCE SUMMARYTimely post-prophase breakdown of the Arabidopsis cyclin CYCA3;4 by the Anaphase Promoting Complex/Cyclosome is essential for meristem organization and development.

plant biology↗