Biology subjects

Albrecht, C.

Publications and source records attributed to Albrecht, C..

10 recordsLinked to original sources

bioRxiv2026

Minimal requirements and evolution of polar membrane targeting in the land plant SOSEKI protein family

Accurate spatial distribution of polar proteins is essential for cell function, but mechanisms underlying polar protein targeting in plants are poorly understood. Here, we dissect the molecular mechanisms underlying the polar targeting of the SOSEKI1 (SOK1) protein in Arabidopsis thaliana. Using extensive mutagenesis and truncation analyses of the polarity domain, we mapped the minimal polarity fragment necessary and sufficient for stable polar targeting to a 25-amino-acid region. This region likely forms an amphipathic helix, and mutations reveal that both its polar and apolar faces are essential for membrane association and polarity. Using phylogenetic analysis, we reconstruct the evolutionary history of the minimal polar targeting region across land plants. Using cross-species expression and protein localization, we infer the ancestral polar SOK localization pattern and show how it remained remarkably conserved, only to diversify upon gene duplication. This work identifies a polar targeting peptide in plants, reveals a mechanism for polar membrane targeting of a plant protein family, and demonstrates both conservation and diversification within this family.

plant biology↗

bioRxiv2026

The cell polarity landscape in Arabidopsis male and female gametophytes

Plant cell polarity underlies the capacity to directionally transport auxin and other small molecules, but also precedes asymmetric cell division in the stomatal lineage. Except for specific contexts, mechanisms underlying cell polarization are poorly understood. Most insights on plant cell polarity have come from studies on flowering plant sporophytes, while no polar protein localization has yet been reported in flowering plant gametophytes, despite clear anisotropic growth and asymmetric cell divisions in this generation. Inspired by the identification of deeply conserved SOSEKI proteins and their associated partners that mark polar domains in bryophyte gametophytes and Arabidopsis sporophytes, we here investigate cell polarity in Arabidopsis gametophytes. We discover a rich landscape of polar domains throughout male and female gametophyte development, marked by one or more polar proteins. We find that successive steps in male gametophyte polarization can be mechanistically uncoupled, and the first polarization step precedes asymmetric cell division. Using ectopic expression, we find that there is a near-universal capacity for polar protein localization in gametophytes through a single polarity system. Our work offers the first insight into gametophyte cell polarity in Arabidopsis, identifies novel polar domains, and presents a starting point for future dissection of mechanisms underlying plant cell polarity.

plant biology↗

bioRxiv2026

Systematic proteomics identifies a conserved mechanism for polar targeting of plant cortical proteins

Multicellular development is tightly coupled to the polarization of individual cells, which partitions polar proteins along the cell cortex and can control asymmetric cell division, anisotropic growth, local differentiation or physiology. Mechanisms driving cell polarization have been described in fungi and animals, but these lack counterparts in plants. While several polarized proteins have been identified in plants, the overall mechanisms guiding their polar localization are poorly characterized. Through iterative affinity proteomics on the recently identified SOSEKI polar proteins, we discovered a network of polar proteins that is conserved in the flowering plant Arabidopsis and the liverwort Marchantia. We next used this collection of novel polarized proteins for systematic proximity ligation proteomics in these two species to map their global polar proteome. We identified a subfamily of polarized Protein S-acyl transferase (PAT) enzymes that are required for membrane targeting of Arabidopsis SOSEKI proteins. Using human and fruit fly models, we showed that PAT19 is sufficient for membrane targeting of SOSEKI1, likely through direct palmitoylation. This work demonstrates a conserved mechanism for polar protein targeting in plants and offers a resource for studying polar protein localization.

plant biology↗

bioRxiv2026

A primary human muscle cell-based assay for detecting myasthenia gravis autoantibody binding and assessing AChR cluster impairment

Myasthenia gravis (MG) is an autoimmune disease caused by pathogenic autoantibodies against proteins at the neuromuscular junction (NMJ). The diagnosis and clinical management of MG patients largely relies on the detection of antigen-specific autoantibodies targeting acetylcholine receptor (AChR) or muscle-specific kinase (MuSK). Yet a subset of patients remains seronegative for known MG autoantibodies, highlighting a critical need for alternative approaches to identify pathogenic NMJ antibodies. We established a new human in vitro model of the NMJ based on primary human muscle cells that recapitulates key features of the NMJ: differentiation to myotubes, expression of key NMJ proteins and formation of postsynaptic AChR clusters in response to agrin stimulation. The model allows new insights into myogenesis and genetic muscle diseases, and the new muscle cell-based assay (CBA) detected autoantibodies in sera from patients with AChR- and MuSK-positive MG with 96.43% sensitivity and 100% specificity, while healthy control sera showed no reactivity. Incubation with patient sera significantly reduced AChR clustering compared to controls, demonstrating functional pathogenic effects. Thus, we established a physiologically relevant human NMJ model that enables detection and functional characterization of neuromuscular autoantibodies. This novel approach addresses a key limitation of current antigen-specific diagnostics and provides a method for improved detection and characterization of MG antibodies, independent of antigen specificity. One Sentence SummaryWe established a postsynaptic human in vitro neuromuscular junction model to assess binding and pathogenicity of MG autoantibodies. Key messagesO_ST_ABSWhat is already known on this topic?C_ST_ABSCurrent diagnosis of myasthenia gravis (MG) relies largely on the detection of antigen-specific autoantibodies against AChR and MuSK, leaving a clinically relevant subset of patients seronegative. What are the new findings?We established a physiologically relevant human in vitro neuromuscular junction model based on primary human muscle cells and developed a novel muscle cell-based assay (CBA) for the detection of neuromuscular autoantibodies. How might this impact on clinical practice or future developments?The CBA detected autoantibodies in patients with AChR- or MuSK-positive MG with high sensitivity and specificity and demonstrated their functional pathogenic effects on AChR clustering. This antigen-independent approach may improve the detection and functional characterization of MG autoantibodies, particularly in patients who are seronegative in current diagnostic assays. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=130 SRC="FIGDIR/small/743478v1_ufig1.gif" ALT="Figure 1000"> View larger version (38K): org.highwire.dtl.DTLVardef@c2e1fforg.highwire.dtl.DTLVardef@8336fforg.highwire.dtl.DTLVardef@8fa2b0org.highwire.dtl.DTLVardef@1d94e_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2026

High resolution, proteome-wide mapping of subcellular protein localization in plants

Protein function is intimately connected to subcellular localization, and experimental determination of protein localization is a key element of understanding biological roles. However, even in the best-studied model plants, such as Arabidopsis thaliana, a minority of proteins has an experimentally defined subcellular localization. We present an experimental strategy to globally map plant subcellular proteomes by mass spectrometry. We annotated subcellular localization of 7815 proteins in Arabidopsis roots, 4672 in Arabidopsis seedlings, and 2782 in the liverwort Marchantia polymorpha. By independent validation, we find that these annotations are highly predictive and can be integrated with other proteomics datasets. Cross-species comparisons reveal substantial global conservation of subcellular localization. Furthermore, we demonstrate that the same approach can be used to identify dynamically translocating proteins upon treatment or in a mutant. This work shows the power of global spatial proteome mapping in plants and offers an extensive resource for protein subcellular localization in plants. HighlightsO_LIOptimized approach for global mapping of protein subcellular localization by differential centrifugation in plants C_LIO_LIInteractive resource of subcellular localization of plant proteins at unprecedented depth and resolution C_LIO_LICross-species comparison reveals that the plant subcellular proteome is deeply conserved C_LIO_LIComparative subcellular proteomics of a Brefeldin A treatment and a gnom mutant robustly describes global shifts in protein localization C_LI

plant biology↗

bioRxiv2025

Transcranial direct current stimulation over the frontal eye field has no effect on visual search performance

Top-down attention for the goal-directed (de-)prioritization of information is fundamental for successful everyday-life behavior and poses tremendous problems when negatively impacted by disease. Attention-targeting enhancement and rehabilitation attempts using non-invasive brain stimulation techniques like transcranial direct current stimulation (tDCS) are therefore of major importance. tDCS-driven excitation of the left frontal eye field (FEF; a key region within fronto-parietal attention networks) has recently been suggested to improve attention-guided visual search with stronger effects for lower baseline performers. Here, we report two preregistered tDCS experiments that tested 1) whether the previously observed visual search improvement could be boosted through stimulation over the allegedly more dominant right FEF and 2) whether tDCS-related visual search improvements might depend on search field size. To this end, in experiments one and two, N=29 and N=31 healthy participants performed a visual search task, in which they searched for an upside-down T amongst upright Ts and Ls within small or large search fields, before and during the application of anodal (excitatory) or sham (control) tDCS over the right or left FEF, respectively. In contrast to previous studies, in both experiments (i.e., independent of stimulation site and search field size) we found neither tDCS-specific (anodal > sham) visual search improvements, nor stimulation-specific baseline dependencies (larger improvements for lower baseline performers were observed in both tDCS conditions, suggesting rather stimulation-unspecific effects like regression to the mean). Together, our results provide evidence against reliable top-down attention-guided visual search improvements through FEF tDCS.

neuroscience↗

bioRxiv2024

Mechanism of auxin-dependent gene regulation through composite auxin response elements

The plant signaling molecule auxin controls growth and development, largely through activating and repressing the expression of thousands of genes. Auxin-dependent transcriptional changes are mediated by DNA-binding Auxin Response Factors (ARF), whose AuxRE DNA binding sites are well-known. The identification of the first AuxRE showed this to be part of a composite element with a second motif. Indeed, systematic analysis showed other DNA motifs to be enriched in auxin-regulated promoters. Neither the basis for this enrichment nor the mechanisms for the activity of composite AuxREs is known. Here, we systematically mined Arabidopsis promoters for composite AuxRE elements enriched in auxin-responsive genes. We identified many and show that their presence is a reliable predictor of auxin response. Through mutating these elements and their higher-order modules, we demonstrate function in promoter activity. Lastly, we identified transcription factors (TFs) that bind AuxRE-associated motifs, showed their involvement in auxin response, and discovered that several of these TFs directly bind ARF proteins. We propose that ARF-TF complexes specifically bind compound motifs in promoters, and act as a source of diversification in auxin-dependent gene regulation.

plant biology↗

bioRxiv2023

Prediction of tumor-specific splicing from somatic mutations as a source of neoantigen candidates

Splicing is dysregulated in many tumors and may result in tumor-specific transcripts that can encode neoantigens, which are promising targets for cancer immunotherapy. Detecting tumor-specific splicing is challenging because many non-canonical splice junctions identified in tumor transcriptomes also appear in healthy tissues. Here, we developed splice2neo to integrate the predicted splice effects from somatic mutations with splice junctions detected in tumor RNA-seq for individual cancer patients. Splice2neo excludes splice junctions from healthy tissue samples, annotates resulting transcript and peptide sequences, and provides targeted re-quantification of supporting RNA-seq reads. We developed a stringent detection rule to predict splice junctions as mutation-derived targets and identified 1.7 target splice junctions per tumor with a false discovery rate below 5% in a melanoma cohort. We confirmed tumor-specificity using independent, healthy tissue samples. Furthermore, using tumor-derived RNA, we confirmed individual exon skipping events experimentally. Most target splice junctions encoded neoepitope candidates with predicted MHC-I or MHC-II binding. Compared to neoepitope candidates derived from non-synonymous point mutations, the splicing-derived MHC-I neoepitope candidates had a lower self-similarity to corresponding wild-type peptides. In conclusion, we demonstrate that identifying mutation-derived and tumor-specific splice junctions can lead to additional neoantigen candidates to expand the target repertoire for cancer immunotherapies. Key PointsO_LIsplice2neo is a versatile tool for identifying and analyzing of splice junctions as a source of neoantigen candidates C_LIO_LIWe identified mutation-retrieved splice junctions supported by RNA-seq in melanoma samples C_LIO_LIThe predicted target splice junctions exhibited a strong tumor-specificity as they were absent in healthy tissues. C_LIO_LITarget splice junctions often lead to frame-shift peptides and encode promising neoantigen candidates C_LI

bioinformatics↗

bioRxiv2020

Cryo-EM structures and functional properties of CALHM channels of the human placenta

The transport of substances across the placenta is essential for the development of the fetus. Here, we were interested in the role of channels of the calcium homeostasis modulator (CALHM) family in the human placenta. By transcript analysis, we found the paralogs CALHM2, 4, and 6 to be highly expressed in this organ and upregulated during trophoblast differentiation. Based on electrophysiology, we found that activation of these paralogs differs from the voltage- and calcium-gated channel CALHM1. Cryo-EM structures of CALHM4 display decameric and undecameric assemblies with large cylindrical pore, while in CALHM6 a conformational change has converted the pore shape into a conus that narrows at the intracellular side, thus describing distinct functional states of the channel. The pore geometry alters the distribution of lipids, which occupy the cylindrical pore of CALHM4 in a bilayer-like arrangement whereas they have redistributed in the conical pore of CALHM6 with potential functional consequences.

biophysics↗

bioRxiv2020

Suspensor-derived somatic embryogenesis in Arabidopsis

In many flowering plants, including Arabidopsis thaliana, asymmetric division of the zygote generates apical and basal cells with different fates. The apical cell continues to produce the embryo while the basal cell undergoes a restricted number of anticlinal divisions leading to a suspensor of 6-9 quiescent cells that remain extra-embryonic and eventually senesce. In some genetic backgrounds, or upon ablation of the embryo, suspensor cells can however undergo periclinal cell divisions and eventually form a second, twin seedling. Likewise, embryogenesis can be induced from somatic cells by various genes, but the relation to suspensor-derived embryos is unclear. Here, we addressed the nature of the suspensor to embryo fate transformation, and its genetic triggers. We expressed most known embryogenesis-inducing transcriptional regulators and receptor-like kinases specifically in suspensor cells. Among these, only RKD1 and WUS could induce a heritable twin seedling phenotype. We next analyzed morphology and fate marker expression in embryos in which suspensor division were activated by different triggers to address the developmental paths towards reprogramming. Our results show that reprogramming of Arabidopsis suspensor cells towards embryonic identity is a specific cellular response that is triggered by defined regulators, follows a conserved developmental trajectory and shares similarity to the process of somatic embryogenesis from post-embryonic tissues.

plant biology↗