Biology subjects

Staszewski, J.

Publications and source records attributed to Staszewski, J..

4 recordsLinked to original sources

bioRxiv2025

Comparative functional profiling of plant ACR3 orthologs reveals metalloid-sensitive trafficking and arsenic efflux capabilities

Arsenic contamination poses a major environmental and public health challenge. In liverworts and ferns, ACR3 transporters mediate arsenite efflux and contribute to arsenic tolerance. We recently showed that ACR3 from Marchantia polymorpha (MpACR3) contains an extended N-terminal region that couples arsenic sensing to membrane trafficking. However, the function and regulation of ACR3 transporters across photosynthetic lineages remain unclear. Here, we characterize ACR3 transporters from phylogenetically distant algae and land plants using heterologous expression in yeast. All examined ACR3 proteins function as arsenic efflux transporters but display two distinct trafficking modes: constitutive plasma membrane localization or metalloid-driven relocalization from the endomembrane system. Like the previously characterized MpACR3, we show that this inducible trafficking is governed by an extended N-terminal domain unique to plant ACR3 proteins, integrating a conserved di-arginine ER/Golgi retention signal with cysteine-based arsenic sensing. These findings establish a direct mechanistic link between metalloid perception and subcellular targeting. Functional assays in Arabidopsis thaliana demonstrated that Physcomitrium patens ACR3 confers arsenic tolerance, reduces root arsenic accumulation, and retains metalloid-dependent trafficking, supporting its physiological relevance. Together, our findings uncover a conserved mechanism linking arsenic sensing to ACR3 trafficking and provide new insight into the evolution of arsenic tolerance in plants. Summary statementPlant ACR3 transporters mediate arsenic efflux and exhibit distinct trafficking modes. An N-terminal domain links arsenic sensing to the endomembrane system-plasma membrane relocalization, revealing a conserved mechanism controlling ACR3 function and arsenic tolerance across plant lineages.

plant biology↗

bioRxiv2025

Arsenic-sensing domain controls ACR3 transporter trafficking and function in Marchantia polymorpha

Arsenic, a toxic and carcinogenic metalloid, is a pervasive environmental contaminant that threatens human health through contaminated water and food. The efflux of As(III) via ACR3 transporters is an ancient detoxification mechanism conserved across prokaryotes, fungi, and plants, with the notable exception of angiosperms. Despite their evolutionary significance, plant ACR3s remain largely uncharacterized. Here, we demonstrate that MpACR3, the ACR3 orthologue from the liverwort Marchantia polymorpha, functions as a metalloid/proton antiporter, conferring resistance to arsenicals and moderate tolerance to antimony. Additionally, we uncover an arsenic-sensing domain within MpACR3 that regulates its intracellular trafficking. Under normal conditions, MpACR3 sorting to the plasma membrane is delayed, resulting in its retention within Golgi bodies. However, As(III) binding to three cysteine residues in the N-terminal cytosolic domain induces a conformational change that facilitates MpACR3 trafficking to the plasma membrane. Furthermore, mutational analysis of a conserved arginine-based motif reveals that the N-terminal domain not only controls MpACR3 accumulation at the plasma membrane but also modulates its transport activity. Importantly, this arsenic-sensing domain is conserved among plant ACR3 transporters, suggesting a plant-specific adaptation to arsenic toxicity.

plant biology↗

bioRxiv2017

Risk factor profile of different clinical manifestations of cerebral small vessel disease - data from SHEF-CSVD Study.

BACKGROUNDLittle is known of the mechanisms of cerebral small vessel disease (CSVD). Both atherosclerosis or non-atherosclerotic diffuse arteriopathy are involved.\n\nMETHODSA single-center, prospective, case-control study was performed in consecutive patients with different CSVD manifestations. The study group consisted of 205 patients: 52 with lacunar stroke (LS), 20 with subcortical hemorrhagic stroke (HS), 50 with vascular dementia (VaD), 28 with vascular parkinsonism (VaP) and 55 controls (CG) free of cerebrovascular disease but with high vascular risk.\n\nRESULTSPatients with CSVD had significantly higher prevalence of vascular risk factors including hypertension, diabetes mellitus, polymetabolic syndrome and chronic kidney disease. Patients with CSVD had also significantly higher fasting blood glucose, homocysteine, fibrinogen, systolic blood pressure, IMT values and lower eGFR, albumin and HDL levels. After adjustment for age and sex, low eGFR, albumin and high levels of uric acid and fibrinogen were associated with all CSVD groups, elevated fasting glucose was related to LS and HS. In the multivariate analysiss, the independent predictors for CSVD were female sex, low albumin, high fibrinogen, fasting glucose and uric acid. Patients with LS had significantly higher IMT values comparing to other CSVD groups, patients with VaP had a trend towards higher homocysteine levels.\n\nCONCLUSIONRisk factor profile for CSVD as a whole differs from subjects with proatherogenic profile without history of cerebrovascular disease. Our results support the concept that CSVD is not homogeneous, and that unique risk factors profiles exist for different clinical manifestations of the disease.

neuroscience↗

bioRxiv2017

Risk of vascular events or death in different manifestations of cerebral small vessel disease: a 2-year follow-up study with a control group

Background and PurposeNatural course of cerebral small vessel disease (CSVD) has not yet been thoroughly studied. The aim of the single center study was to establish risk of vascular events or death in different manifestations of CSVD.\n\nMethods150 consecutive, functionally independent patients with marked MRI features of CSVD and with recent lacunar stroke (n=52, LS), 20 with deep hemorrhagic stroke (HS), 28 with vascular parkinsonism (VaP), 50 with vascular dementia (VaD) and 55 controls (CG) with high atherothrombotic risk free of cerebrovascular events were prospectively recruited and followed for 24 months.\n\nResultsMean age and sex distribution were similar in CSVD and CG but patients with CSVD were less likely to have CAD (19% vs 40%, p=0,02) and tended to have higher prevalence of diabetes (54% vs 37%, p=0,11). The risk of vascular events or death was increased in any patients with moderate to severe white matter lesions at baseline MRI (HR 2,0; 95%CI 0,85-7,2), in CSVD (4,56; 95%CI 1,3-14,9) vs CG, regardless of its clinical manifestation: LS or HS (HR 4,70; 95%CI 1,3-16,2) and VaD or VaP (HR 4,59; 95%CI 1,3-15,7).\n\nConclusionsPatients with symptomatic CSVD regardless of the clinical (acute or chronic) manifestation had more than fourfold the risk of vascular events or death in 24 months of observation compared with controls with high atherothrombotic risk free of cerebrovascular events.

neuroscience↗