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2. Alternative splicing regulates stochastic NLRP3 activity.

Author

Hoss, Florian, Mueller, James L, Rojas Ringeling, Francisca, Rodriguez-Alcazar, Juan F, Brinkschulte, Rebecca, Seifert, Gerald, Stahl, Rainer, Broderick, Lori, Putnam, Chris D, Kolodner, Richard D, Canzar, Stefan, Geyer, Matthias, Hoffman, Hal M, and Latz, Eicke

Subjects
Cells, Cultured, Macrophages, Animals, Swine, Humans, Neoplasm Proteins, Protein Isoforms, Stochastic Processes, Alternative Splicing, Amino Acid Sequence, Exons, Immunity, Innate, HEK293 Cells, Inflammasomes, NIMA-Related Kinases, NLR Family, Pyrin Domain-Containing 3 Protein, Protein Domains, Cells, Cultured, Immunity, Innate, NLR Family, Pyrin Domain-Containing 3 Protein
Abstract

Leucine-rich repeat (LRR) domains are evolutionarily conserved in proteins that function in development and immunity. Here we report strict exonic modularity of LRR domains of several human gene families, which is a precondition for alternative splicing (AS). We provide evidence for AS of LRR domain within several Nod-like receptors, most prominently the inflammasome sensor NLRP3. Human NLRP3, but not mouse NLRP3, is expressed as two major isoforms, the full-length variant and a variant lacking exon 5. Moreover, NLRP3 AS is stochastically regulated, with NLRP3 ∆ exon 5 lacking the interaction surface for NEK7 and hence loss of activity. Our data thus reveals unexpected regulatory roles of AS through differential utilization of LRRs modules in vertebrate innate immunity.

Published
2019

7. Dysfunction of NG2 glial cells affects neuronal plasticity and behavior

Author

Timmermann, Aline, primary, Tascio, Dario, additional, Jabs, Ronald, additional, Boehlen, Anne, additional, Domingos, Catia, additional, Skubal, Magdalena, additional, Huang, Wenhui, additional, Kirchhoff, Frank, additional, Henneberger, Christian, additional, Bilkei‐Gorzo, Andras, additional, Seifert, Gerald, additional, and Steinhäuser, Christian, additional

Published
2023
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10. Impact of Developmental Changes of GABA A Receptors on Interneuron-NG2 Glia Transmission in the Hippocampus.

Author

Patt, Linda, Tascio, Dario, Domingos, Catia, Timmermann, Aline, Jabs, Ronald, Henneberger, Christian, Steinhäuser, Christian, and Seifert, Gerald

Subjects
GABA receptors, AMPA receptors, HIPPOCAMPAL innervation, HIPPOCAMPUS (Brain), EXPANSION microscopy, SOMATOSENSORY cortex, INNERVATION
Abstract

NG2 glia receive synaptic input from neurons, but the functional impact of this glial innervation is not well understood. In the developing cerebellum and somatosensory cortex the GABAergic input might regulate NG2 glia differentiation and myelination, and a switch from synaptic to extrasynaptic neuron–glia signaling was reported in the latter region. Myelination in the hippocampus is sparse, and most NG2 glia retain their phenotype throughout adulthood, raising the question of the properties and function of neuron-NG2 glia synapses in that brain region. Here, we compared spontaneous and evoked GABAA receptor-mediated currents of NG2 glia in juvenile and adult hippocampi of mice of either sex and assessed the mode of interneuron–glial signaling changes during development. With patch-clamp and pharmacological analyses, we found a decrease in innervation of hippocampal NG2 glia between postnatal days 10 and 60. At the adult stage, enhanced activation of extrasynaptic receptors occurred, indicating a spillover of GABA. This switch from synaptic to extrasynaptic receptor activation was accompanied by downregulation of γ2 and upregulation of the α5 subunit. Molecular analyses and high-resolution expansion microscopy revealed mechanisms of glial GABAA receptor trafficking and clustering. We found that gephyrin and radixin are organized in separate clusters along glial processes. Surprisingly, the developmental loss of γ2 and postsynaptic receptors were not accompanied by altered glial expression of scaffolding proteins, auxiliary receptor subunits or postsynaptic interaction proteins. The GABAergic input to NG2 glia might contribute to the release of neurotrophic factors from these cells and influence neuronal synaptic plasticity. [ABSTRACT FROM AUTHOR]

Published
2023
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12. Reactive microglia are the major source of tumor necrosis factor alpha and contribute to astrocyte dysfunction and acute seizures in experimental temporal lobe epilepsy

Author

Henning, Lukas, primary, Antony, Henrike, additional, Breuer, Annika, additional, Müller, Julia, additional, Seifert, Gerald, additional, Audinat, Etienne, additional, Singh, Parmveer, additional, Brosseron, Frederic, additional, Heneka, Michael T., additional, Steinhäuser, Christian, additional, and Bedner, Peter, additional

Published
2022
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41. KIAA1797/FOCAD encodes a novel focal adhesion protein with tumour suppressor function in gliomas

Author

Brockschmidt, Antje, Trost, Detlef, Peterziel, Heike, Zimmermann, Katrin, Ehrler, Marion, Grassmann, Henriette, Pfenning, Philipp-Niclas, Waha, Anke, Wohlleber, Dirk, Brockschmidt, Felix F., Jugold, Manfred, Hoischen, Alexander, Kalla, Claudia, Waha, Andreas, Seifert, Gerald, Knolle, Percy A., Latz, Eicke, Hans, Volkmar H., Wick, Wolfgang, Pfeifer, Alexander, Angel, Peter, and Weber, Ruthild G.

Published
2012
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