Lehrstuhl für Biotechnologie und Biophysik

Biophysics of Fungi & Optogenetics

Protein Engineering & Dynamics

Collaborative Research Center / Transregio 166
High-end light microscopy elucidates membrane receptor function

In the CRC/TRR 166 ReceptorLight high-end light microscopy techniques with highest spatial and time resolution are applied and further developed to gain deeper insight into the function of membrane receptors. The participating groups in Jena and Würzburg bundle their methodological expertise in the field of super-resolution microscopy, electrophysiology, and biophysics of membrane receptors to generate new insights into the function and distribution of diverse membrane receptors, and in parallel, to induce the development of new high-end light-microscopy methods.

For more informations see receptorlight

Center for Personalized Molecular Immunotherapy

The European Structural Fund supports two new projects of the University of Würzburg with more than EUR 4.3 million. In close cooperation with the University Hospital and regional companies, research activities aim to drive medical progress.

"The Bavarian State Ministry for Education, Science and the Arts funds two seminal projects which the University of Würzburg runs jointly with regional companies by providing more than EUR 4.3 million in total from funds of the European Regional Development Fund", Bavarian Minister of State, Dr Ludwig Spaenle, announced a few days ago. more >>

Light-induced cell damage in live-cell super-resolution microscopy

Super-resolution microscopy can unravel previously hidden details of cellular structures but requires high irradiation intensities to use the limited photon budget efficiently. Such high photon densities are likely to induce cellular damage in live-cell experiments. more >>

Latest Publications

Decoding the molecular interplay of CD20 and therapeutic antibodies with fast volumetric nanoscopy. Ghosh, Arindam; Meub, Mara; Helmerich, Dominic A.; Weingart, Julia; Eiring, Patrick; Nerreter, Thomas; Kortüm, K. Martin; Doose, Sören; Sauer, Markus. In Science, 387(6730), S. eadq4510-. American Association for the Advancement of Science, 2025.
- [ Abstract ]
- [ BibTeX ]
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Elucidating the interaction between membrane proteins and antibodies requires whole-cell imaging at high spatiotemporal resolution. Lattice light-sheet (LLS) microscopy offers fast volumetric imaging but suffers from limited spatial resolution. DNA-based point accumulation for imaging in nanoscale topography (DNA-PAINT) achieves molecular resolution but is restricted to two-dimensional imaging owing to long acquisition times. We have developed two-dye imager (TDI) probes that enable ~15-fold faster imaging. Combining TDI-DNA-PAINT and LLS microscopy on immunological B cells revealed the oligomeric states and interaction of endogenous CD20 with the therapeutic monoclonal antibodies (mAbs) rituximab, ofatumumab, and obinutuzumab. Our results demonstrate that CD20 is abundantly expressed on microvilli that bind mAbs, which leads to an antibody concentration?dependent B cell polarization and stabilization of microvilli protrusions. These findings could aid rational design of improved immunotherapies targeting tumor-associated antigens. Therapeutic monoclonal antibodies (mAbs) are used in chronic lymphocytic leukemia immunotherapies to target the receptor CD20 at the plasma membrane of immunological B cells. Although they have been in clinical use for several years, the molecular binding mechanisms of mAbs to endogenous CD20 are unclear, as is how antibody binding activates the immune system to kill B cells. Ghosh et al. developed a method for fast volumetric fluorescence imaging with high spatiotemporal resolution that reveals the accumulation of CD20/mAb complexes on the microvilli of polarized B cells. The results show that the classification criterion of anti-CD20 mAbs based on their receptor cross-linking efficiency needs revision. Such high-end imaging techniques should help in the development of improved immunotherapies. ?Stella M. Hurtley

@article{ghoshdecoding, abstract = {Elucidating the interaction between membrane proteins and antibodies requires whole-cell imaging at high spatiotemporal resolution. Lattice light-sheet (LLS) microscopy offers fast volumetric imaging but suffers from limited spatial resolution. DNA-based point accumulation for imaging in nanoscale topography (DNA-PAINT) achieves molecular resolution but is restricted to two-dimensional imaging owing to long acquisition times. We have developed two-dye imager (TDI) probes that enable 15-fold faster imaging. Combining TDI-DNA-PAINT and LLS microscopy on immunological B cells revealed the oligomeric states and interaction of endogenous CD20 with the therapeutic monoclonal antibodies (mAbs) rituximab, ofatumumab, and obinutuzumab. Our results demonstrate that CD20 is abundantly expressed on microvilli that bind mAbs, which leads to an antibody concentration?dependent B cell polarization and stabilization of microvilli protrusions. These findings could aid rational design of improved immunotherapies targeting tumor-associated antigens. Therapeutic monoclonal antibodies (mAbs) are used in chronic lymphocytic leukemia immunotherapies to target the receptor CD20 at the plasma membrane of immunological B cells. Although they have been in clinical use for several years, the molecular binding mechanisms of mAbs to endogenous CD20 are unclear, as is how antibody binding activates the immune system to kill B cells. Ghosh et al. developed a method for fast volumetric fluorescence imaging with high spatiotemporal resolution that reveals the accumulation of CD20/mAb complexes on the microvilli of polarized B cells. The results show that the classification criterion of anti-CD20 mAbs based on their receptor cross-linking efficiency needs revision. Such high-end imaging techniques should help in the development of improved immunotherapies. ?Stella M. Hurtley}, author = {Ghosh, Arindam and Meub, Mara and Helmerich, Dominic A. and Weingart, Julia and Eiring, Patrick and Nerreter, Thomas and Kortüm, K. Martin and Doose, Sören and Sauer, Markus}, booktitle = {Science}, journal = {Science}, keywords = {home}, number = 6730, pages = {eadq4510–}, publisher = {American Association for the Advancement of Science}, title = {Decoding the molecular interplay of CD20 and therapeutic antibodies with fast volumetric nanoscopy}, volume = 387, year = 2025 }

%0 Journal Article %1 ghoshdecoding %A Ghosh, Arindam %A Meub, Mara %A Helmerich, Dominic A. %A Weingart, Julia %A Eiring, Patrick %A Nerreter, Thomas %A Kortüm, K. Martin %A Doose, Sören %A Sauer, Markus %B Science %D 2025 %I American Association for the Advancement of Science %J Science %N 6730 %P eadq4510-- %R 10.1126/science.adq4510 %T Decoding the molecular interplay of CD20 and therapeutic antibodies with fast volumetric nanoscopy %U https://doi.org/10.1126/science.adq4510 %V 387 %X Elucidating the interaction between membrane proteins and antibodies requires whole-cell imaging at high spatiotemporal resolution. Lattice light-sheet (LLS) microscopy offers fast volumetric imaging but suffers from limited spatial resolution. DNA-based point accumulation for imaging in nanoscale topography (DNA-PAINT) achieves molecular resolution but is restricted to two-dimensional imaging owing to long acquisition times. We have developed two-dye imager (TDI) probes that enable ~15-fold faster imaging. Combining TDI-DNA-PAINT and LLS microscopy on immunological B cells revealed the oligomeric states and interaction of endogenous CD20 with the therapeutic monoclonal antibodies (mAbs) rituximab, ofatumumab, and obinutuzumab. Our results demonstrate that CD20 is abundantly expressed on microvilli that bind mAbs, which leads to an antibody concentration?dependent B cell polarization and stabilization of microvilli protrusions. These findings could aid rational design of improved immunotherapies targeting tumor-associated antigens. Therapeutic monoclonal antibodies (mAbs) are used in chronic lymphocytic leukemia immunotherapies to target the receptor CD20 at the plasma membrane of immunological B cells. Although they have been in clinical use for several years, the molecular binding mechanisms of mAbs to endogenous CD20 are unclear, as is how antibody binding activates the immune system to kill B cells. Ghosh et al. developed a method for fast volumetric fluorescence imaging with high spatiotemporal resolution that reveals the accumulation of CD20/mAb complexes on the microvilli of polarized B cells. The results show that the classification criterion of anti-CD20 mAbs based on their receptor cross-linking efficiency needs revision. Such high-end imaging techniques should help in the development of improved immunotherapies. ?Stella M. Hurtley
Small fibre neuropathy in Fabry disease: a human-derived neuronal in vitro disease model and pilot data. Klein, Thomas; Grüner, Julia; Breyer, Maximilian; Schlegel, Jan; Schottmann, Nicole Michelle; Hofmann, Lukas; Gauss, Kevin; Mease, Rebecca; Erbacher, Christoph; Finke, Laura; Klein, Alexandra; Klug, Katharina; Karl-Schöller, Franziska; Vignolo, Bettina; Reinhard, Sebastian; Schneider, Tamara; Günther, Katharina; Fink, Julian; Dudek, Jan; Maack, Christoph; Klopocki, Eva; Seibel, Jürgen; Edenhofer, Frank; Wischmeyer, Erhard; Sauer, Markus; Üçeyler, Nurcan. In Brain Communications, 6(2), S. fcae095-. 2024.
- [ Abstract ]
- [ BibTeX ]
- [ EndNote ]
- [ URL ]
Acral burning pain triggered by fever, thermal hyposensitivity and skin denervation are hallmarks of small fibre neuropathy in Fabry disease, a life-threatening X-linked lysosomal storage disorder. Variants in the gene encoding alpha-galactosidase A may lead to impaired enzyme activity with cellular accumulation of globotriaosylceramide. To study the underlying pathomechanism of Fabry-associated small fibre neuropathy, we generated a neuronal in vitro disease model using patient-derived induced pluripotent stem cells from three Fabry patients and one healthy control. We further generated an isogenic control line via gene editing. We subjected induced pluripotent stem cells to targeted peripheral neuronal differentiation and observed intra-lysosomal globotriaosylceramide accumulations in somas and neurites of Fabry sensory neurons using super-resolution microscopy. At functional level, patch-clamp analysis revealed a hyperpolarizing shift of voltage-gated sodium channel steady-state inactivation kinetics in isogenic control neurons compared with healthy control neurons (P < 0.001). Moreover, we demonstrate a drastic increase in Fabry sensory neuron calcium levels at 39°C mimicking clinical fever (P < 0.001). This pathophysiological phenotype was accompanied by thinning of neurite calibres in sensory neurons differentiated from induced pluripotent stem cells derived from Fabry patients compared with healthy control cells (P < 0.001). Linear–nonlinear cascade models fit to spiking responses revealed that Fabry cell lines exhibit altered single neuron encoding properties relative to control. We further observed mitochondrial aggregation at sphingolipid accumulations within Fabry sensory neurites utilizing a click chemistry approach together with mitochondrial dysmorphism compared with healthy control cells. We pioneer pilot insights into the cellular mechanisms contributing to pain, thermal hyposensitivity and denervation in Fabry small fibre neuropathy and pave the way for further mechanistic in vitro studies in Fabry disease and the development of novel treatment approaches.

@article{klein2024small, abstract = {Acral burning pain triggered by fever, thermal hyposensitivity and skin denervation are hallmarks of small fibre neuropathy in Fabry disease, a life-threatening X-linked lysosomal storage disorder. Variants in the gene encoding alpha-galactosidase A may lead to impaired enzyme activity with cellular accumulation of globotriaosylceramide. To study the underlying pathomechanism of Fabry-associated small fibre neuropathy, we generated a neuronal in vitro disease model using patient-derived induced pluripotent stem cells from three Fabry patients and one healthy control. We further generated an isogenic control line via gene editing. We subjected induced pluripotent stem cells to targeted peripheral neuronal differentiation and observed intra-lysosomal globotriaosylceramide accumulations in somas and neurites of Fabry sensory neurons using super-resolution microscopy. At functional level, patch-clamp analysis revealed a hyperpolarizing shift of voltage-gated sodium channel steady-state inactivation kinetics in isogenic control neurons compared with healthy control neurons (P < 0.001). Moreover, we demonstrate a drastic increase in Fabry sensory neuron calcium levels at 39°C mimicking clinical fever (P < 0.001). This pathophysiological phenotype was accompanied by thinning of neurite calibres in sensory neurons differentiated from induced pluripotent stem cells derived from Fabry patients compared with healthy control cells (P < 0.001). Linear–nonlinear cascade models fit to spiking responses revealed that Fabry cell lines exhibit altered single neuron encoding properties relative to control. We further observed mitochondrial aggregation at sphingolipid accumulations within Fabry sensory neurites utilizing a click chemistry approach together with mitochondrial dysmorphism compared with healthy control cells. We pioneer pilot insights into the cellular mechanisms contributing to pain, thermal hyposensitivity and denervation in Fabry small fibre neuropathy and pave the way for further mechanistic in vitro studies in Fabry disease and the development of novel treatment approaches.}, author = {Klein, Thomas and Grüner, Julia and Breyer, Maximilian and Schlegel, Jan and Schottmann, Nicole Michelle and Hofmann, Lukas and Gauss, Kevin and Mease, Rebecca and Erbacher, Christoph and Finke, Laura and Klein, Alexandra and Klug, Katharina and Karl-Schöller, Franziska and Vignolo, Bettina and Reinhard, Sebastian and Schneider, Tamara and Günther, Katharina and Fink, Julian and Dudek, Jan and Maack, Christoph and Klopocki, Eva and Seibel, Jürgen and Edenhofer, Frank and Wischmeyer, Erhard and Sauer, Markus and Üçeyler, Nurcan}, journal = {Brain Communications}, keywords = {home}, month = {04}, number = 2, pages = {fcae095–}, title = {Small fibre neuropathy in Fabry disease: a human-derived neuronal in vitro disease model and pilot data}, volume = 6, year = 2024 }

%0 Journal Article %1 klein2024small %A Klein, Thomas %A Grüner, Julia %A Breyer, Maximilian %A Schlegel, Jan %A Schottmann, Nicole Michelle %A Hofmann, Lukas %A Gauss, Kevin %A Mease, Rebecca %A Erbacher, Christoph %A Finke, Laura %A Klein, Alexandra %A Klug, Katharina %A Karl-Schöller, Franziska %A Vignolo, Bettina %A Reinhard, Sebastian %A Schneider, Tamara %A Günther, Katharina %A Fink, Julian %A Dudek, Jan %A Maack, Christoph %A Klopocki, Eva %A Seibel, Jürgen %A Edenhofer, Frank %A Wischmeyer, Erhard %A Sauer, Markus %A Üçeyler, Nurcan %D 2024 %J Brain Communications %N 2 %P fcae095-- %R 10.1093/braincomms/fcae095 %T Small fibre neuropathy in Fabry disease: a human-derived neuronal in vitro disease model and pilot data %U https://doi.org/10.1093/braincomms/fcae095 %V 6 %X Acral burning pain triggered by fever, thermal hyposensitivity and skin denervation are hallmarks of small fibre neuropathy in Fabry disease, a life-threatening X-linked lysosomal storage disorder. Variants in the gene encoding alpha-galactosidase A may lead to impaired enzyme activity with cellular accumulation of globotriaosylceramide. To study the underlying pathomechanism of Fabry-associated small fibre neuropathy, we generated a neuronal in vitro disease model using patient-derived induced pluripotent stem cells from three Fabry patients and one healthy control. We further generated an isogenic control line via gene editing. We subjected induced pluripotent stem cells to targeted peripheral neuronal differentiation and observed intra-lysosomal globotriaosylceramide accumulations in somas and neurites of Fabry sensory neurons using super-resolution microscopy. At functional level, patch-clamp analysis revealed a hyperpolarizing shift of voltage-gated sodium channel steady-state inactivation kinetics in isogenic control neurons compared with healthy control neurons (P < 0.001). Moreover, we demonstrate a drastic increase in Fabry sensory neuron calcium levels at 39°C mimicking clinical fever (P < 0.001). This pathophysiological phenotype was accompanied by thinning of neurite calibres in sensory neurons differentiated from induced pluripotent stem cells derived from Fabry patients compared with healthy control cells (P < 0.001). Linear–nonlinear cascade models fit to spiking responses revealed that Fabry cell lines exhibit altered single neuron encoding properties relative to control. We further observed mitochondrial aggregation at sphingolipid accumulations within Fabry sensory neurites utilizing a click chemistry approach together with mitochondrial dysmorphism compared with healthy control cells. We pioneer pilot insights into the cellular mechanisms contributing to pain, thermal hyposensitivity and denervation in Fabry small fibre neuropathy and pave the way for further mechanistic in vitro studies in Fabry disease and the development of novel treatment approaches.
LGI1 Autoantibodies Enhance Synaptic Transmission by Presynaptic Kv1 Loss and Increased Action Potential Broadening. Ritzau-Jost, Andreas; Gsell, Felix; Sell, Josefine; Sachs, Stefan; Montanaro, Jacqueline; Kirmann, Toni; Maaß, Sebastian; Irani, Sarosh R.; Werner, Christian; Geis, Christian; Sauer, Markus; Shigemoto, Ryuichi; Hallermann, Stefan. In Neurology Neuroimmunology & Neuroinflammation, 11(5), S. e200284-. Wolters Kluwer, 2024.
- [ Abstract ]
- [ BibTeX ]
- [ EndNote ]
- [ URL ]
Background and Objectives: Autoantibodies against the protein leucine-rich glioma inactivated 1 (LGI1) cause the most common subtype of autoimmune encephalitis with predominant involvement of the limbic system, associated with seizures and memory deficits. LGI1 and its receptor ADAM22 are part of a transsynaptic protein complex that includes several proteins involved in presynaptic neurotransmitter release and postsynaptic glutamate sensing. Autoantibodies against LGI1 increase excitatory synaptic strength, but studies that genetically disrupt the LGI1-ADAM22 complex report a reduction in postsynaptic glutamate receptor-mediated responses. Thus, the mechanisms underlying the increased synaptic strength induced by LGI1 autoantibodies remain elusive, and the contributions of presynaptic molecules to the LGI1-transsynaptic complex remain unclear. We therefore investigated the presynaptic mechanisms that mediate autoantibody-induced synaptic strengthening. Methods: We studied the effects of patient-derived purified polyclonal LGI1 autoantibodies on synaptic structure and function by combining direct patch-clamp recordings from presynaptic boutons and somata of hippocampal neurons with super-resolution light and electron microscopy of hippocampal cultures and brain slices. We also identified the protein domain mediating the presynaptic effect using domain-specific patient-derived monoclonal antibodies. Results: LGI1 autoantibodies dose-dependently increased short-term depression during high-frequency transmission, consistent with increased release probability. The increased neurotransmission was not related to presynaptic calcium channels because presynaptic Cav2.1 channel density, calcium current amplitude, and calcium channel gating were unaffected by LGI1 autoantibodies. By contrast, application of LGI1 autoantibodies homogeneously reduced Kv1.1 and Kv1.2 channel density on the surface of presynaptic boutons. Direct presynaptic patch-clamp recordings revealed that LGI1 autoantibodies cause a pronounced broadening of the presynaptic action potential. Domain-specific effects of LGI1 autoantibodies were analyzed at the neuronal soma. Somatic action potential broadening was induced by polyclonal LGI1 autoantibodies and patient-derived monoclonal autoantibodies targeting the epitempin domain, but not the leucin-rich repeat domain. Discussion Our results indicate that LGI1 autoantibodies reduce the density of both Kv1.1 and Kv1.2 on presynaptic boutons, without actions on calcium channel density or function, thereby broadening the presynaptic action potential and increasing neurotransmitter release. This study provides a molecular explanation for the neuronal hyperactivity observed in patients with LGI1 autoantibodies.

@article{ritzaujostautoantibodies, abstract = {Background and Objectives: Autoantibodies against the protein leucine-rich glioma inactivated 1 (LGI1) cause the most common subtype of autoimmune encephalitis with predominant involvement of the limbic system, associated with seizures and memory deficits. LGI1 and its receptor ADAM22 are part of a transsynaptic protein complex that includes several proteins involved in presynaptic neurotransmitter release and postsynaptic glutamate sensing. Autoantibodies against LGI1 increase excitatory synaptic strength, but studies that genetically disrupt the LGI1-ADAM22 complex report a reduction in postsynaptic glutamate receptor-mediated responses. Thus, the mechanisms underlying the increased synaptic strength induced by LGI1 autoantibodies remain elusive, and the contributions of presynaptic molecules to the LGI1-transsynaptic complex remain unclear. We therefore investigated the presynaptic mechanisms that mediate autoantibody-induced synaptic strengthening. Methods: We studied the effects of patient-derived purified polyclonal LGI1 autoantibodies on synaptic structure and function by combining direct patch-clamp recordings from presynaptic boutons and somata of hippocampal neurons with super-resolution light and electron microscopy of hippocampal cultures and brain slices. We also identified the protein domain mediating the presynaptic effect using domain-specific patient-derived monoclonal antibodies. Results: LGI1 autoantibodies dose-dependently increased short-term depression during high-frequency transmission, consistent with increased release probability. The increased neurotransmission was not related to presynaptic calcium channels because presynaptic Cav2.1 channel density, calcium current amplitude, and calcium channel gating were unaffected by LGI1 autoantibodies. By contrast, application of LGI1 autoantibodies homogeneously reduced Kv1.1 and Kv1.2 channel density on the surface of presynaptic boutons. Direct presynaptic patch-clamp recordings revealed that LGI1 autoantibodies cause a pronounced broadening of the presynaptic action potential. Domain-specific effects of LGI1 autoantibodies were analyzed at the neuronal soma. Somatic action potential broadening was induced by polyclonal LGI1 autoantibodies and patient-derived monoclonal autoantibodies targeting the epitempin domain, but not the leucin-rich repeat domain. Discussion Our results indicate that LGI1 autoantibodies reduce the density of both Kv1.1 and Kv1.2 on presynaptic boutons, without actions on calcium channel density or function, thereby broadening the presynaptic action potential and increasing neurotransmitter release. This study provides a molecular explanation for the neuronal hyperactivity observed in patients with LGI1 autoantibodies.}, author = {Ritzau-Jost, Andreas and Gsell, Felix and Sell, Josefine and Sachs, Stefan and Montanaro, Jacqueline and Kirmann, Toni and Maaß, Sebastian and Irani, Sarosh R. and Werner, Christian and Geis, Christian and Sauer, Markus and Shigemoto, Ryuichi and Hallermann, Stefan}, booktitle = {Neurology Neuroimmunology & Neuroinflammation}, journal = {Neurology Neuroimmunology & Neuroinflammation}, keywords = {home}, number = 5, pages = {e200284–}, publisher = {Wolters Kluwer}, title = {LGI1 Autoantibodies Enhance Synaptic Transmission by Presynaptic Kv1 Loss and Increased Action Potential Broadening}, volume = 11, year = 2024 }

%0 Journal Article %1 ritzaujostautoantibodies %A Ritzau-Jost, Andreas %A Gsell, Felix %A Sell, Josefine %A Sachs, Stefan %A Montanaro, Jacqueline %A Kirmann, Toni %A Maaß, Sebastian %A Irani, Sarosh R. %A Werner, Christian %A Geis, Christian %A Sauer, Markus %A Shigemoto, Ryuichi %A Hallermann, Stefan %B Neurology Neuroimmunology & Neuroinflammation %D 2024 %I Wolters Kluwer %J Neurology Neuroimmunology & Neuroinflammation %N 5 %P e200284-- %R 10.1212/NXI.0000000000200284 %T LGI1 Autoantibodies Enhance Synaptic Transmission by Presynaptic Kv1 Loss and Increased Action Potential Broadening %U https://doi.org/10.1212/NXI.0000000000200284 %V 11 %X Background and Objectives: Autoantibodies against the protein leucine-rich glioma inactivated 1 (LGI1) cause the most common subtype of autoimmune encephalitis with predominant involvement of the limbic system, associated with seizures and memory deficits. LGI1 and its receptor ADAM22 are part of a transsynaptic protein complex that includes several proteins involved in presynaptic neurotransmitter release and postsynaptic glutamate sensing. Autoantibodies against LGI1 increase excitatory synaptic strength, but studies that genetically disrupt the LGI1-ADAM22 complex report a reduction in postsynaptic glutamate receptor-mediated responses. Thus, the mechanisms underlying the increased synaptic strength induced by LGI1 autoantibodies remain elusive, and the contributions of presynaptic molecules to the LGI1-transsynaptic complex remain unclear. We therefore investigated the presynaptic mechanisms that mediate autoantibody-induced synaptic strengthening. Methods: We studied the effects of patient-derived purified polyclonal LGI1 autoantibodies on synaptic structure and function by combining direct patch-clamp recordings from presynaptic boutons and somata of hippocampal neurons with super-resolution light and electron microscopy of hippocampal cultures and brain slices. We also identified the protein domain mediating the presynaptic effect using domain-specific patient-derived monoclonal antibodies. Results: LGI1 autoantibodies dose-dependently increased short-term depression during high-frequency transmission, consistent with increased release probability. The increased neurotransmission was not related to presynaptic calcium channels because presynaptic Cav2.1 channel density, calcium current amplitude, and calcium channel gating were unaffected by LGI1 autoantibodies. By contrast, application of LGI1 autoantibodies homogeneously reduced Kv1.1 and Kv1.2 channel density on the surface of presynaptic boutons. Direct presynaptic patch-clamp recordings revealed that LGI1 autoantibodies cause a pronounced broadening of the presynaptic action potential. Domain-specific effects of LGI1 autoantibodies were analyzed at the neuronal soma. Somatic action potential broadening was induced by polyclonal LGI1 autoantibodies and patient-derived monoclonal autoantibodies targeting the epitempin domain, but not the leucin-rich repeat domain. Discussion Our results indicate that LGI1 autoantibodies reduce the density of both Kv1.1 and Kv1.2 on presynaptic boutons, without actions on calcium channel density or function, thereby broadening the presynaptic action potential and increasing neurotransmitter release. This study provides a molecular explanation for the neuronal hyperactivity observed in patients with LGI1 autoantibodies.

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Lehrstuhl für Biotechnologie und Biophysik

Super-Resolution Microscopy

Quantification of Receptors

Biophysics of Fungi & Optogenetics

Protein Engineering & Dynamics

Center for Personalized Molecular Immunotherapy

Light-induced cell damage in live-cell super-resolution microscopy

Latest Publications

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Multiple-Labeled Antibodies Behave Like Single Emitters in Photoswitching Buffer

Molecular resolution imaging by post-labeling expansion single-molecule localization microscopy (Ex-SMLM)

High-end Microscopy Refined

Impulse for Research on Fungi

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