A5040856868- Neuroscience and Neuropharmacology Research
- Cellular transport and secretion
- Connexins and lens biology
- Renal Diseases and Glomerulopathies
- Photoreceptor and optogenetics research
- Ion channel regulation and function
- Neuroinflammation and Neurodegeneration Mechanisms
- Neurobiology and Insect Physiology Research
- Retinal Development and Disorders
- RNA regulation and disease
- Neural dynamics and brain function
- Neurogenesis and neuroplasticity mechanisms
- Genetics and Neurodevelopmental Disorders
- Mitochondrial Function and Pathology
- Genetic Neurodegenerative Diseases
- Receptor Mechanisms and Signaling
- Lipid metabolism and disorders
- Neuroscience of respiration and sleep
- Heat shock proteins research
- Barrier Structure and Function Studies
- Genetic and Kidney Cyst Diseases
- Congenital Heart Disease Studies
- Sodium Intake and Health
- Cardiovascular Health and Disease Prevention
- Hippo pathway signaling and YAP/TAZ
University of Münster
2011-2023
University Hospital Münster
2020
Stanford University
2016
University of Göttingen
1993-2007
Leibniz Institute for Neurobiology
2005
The University of Texas Southwestern Medical Center
1996-2004
University of Tübingen
1992
gp330/megalin, a member of the low density lipoprotein (LDL) receptor gene family, is expressed on apical surfaces epithelial tissues, including neuroepithelium, where it mediates endocytic uptake diverse macromolecules, such as cholesterol-carrying lipoproteins, proteases, and antiproteinases. Megalin knockout mice manifest abnormalities in tissues lung kidney that normally express protein they die perinatally from respiratory insufficiency. In brain, impaired proliferation neuroepithelium...
The multifunctional low density lipoprotein (LDL) receptor-related protein (LRP) has been postulated to participate in a number of diverse physiological and pathological processes ranging from the homeostasis plasma lipoproteins, atherosclerosis, fibrinolysis neuronal regeneration survival. It not possible demonstrate vivo significance LRP for each these complex by conventional gene knockout approach because is essential embryonic development. Here we have used Cre/loxP recombination system...
AbstractThe LDL receptor-related protein 1 (LRP1) is a multifunctional cell surface receptor that highly expressed on neurons. Neuronal LRP1 in vitro can mediate ligand endocytosis, as well modulate signal transduction processes. However, little known about its role the intact nervous system. Here, we report mice lack selectively differentiated neurons develop severe behavioral and motor abnormalities, including hyperactivity, tremor, dystonia. Since their central systems appear...
Neurexins constitute a large family of highly variable cell-surface molecules that may function in synaptic transmission and/or synapse formation. Each the three known neurexin genes encodes two major variants, alpha- and beta-neurexins, are composed distinct extracellular domains linked to identical intracellular sequences. Deletions one, two, or all alpha-neurexins mice recently demonstrated their essential role at synapses. In multiple alpha-neurexin knock-outs, neurotransmitter release...
Human genetics has identified rare copy number variations and deleterious mutations for all neurexin genes (NRXN1-3) in patients with neurodevelopmental diseases, electrophysiological recordings animal brains have shown that Nrxns are important synaptic transmission. While several mouse models Nrxn1α inactivation previously been studied behavioral changes, very little information is available other variants. Here, we validate mice lacking Nrxn2α exhibit abnormalities, characterized by social...
Abstract Multiple trans-synaptic complexes organize synapse development, yet their roles in the mature brain and cooperation remain unclear. We analyzed postsynaptic adhesion protein LRRTM1 prefrontal cortex (PFC), a region relevant to cognition disorders. knockout (KO) mice had fewer synapses, we asked whether other organizers counteract further loss. This determined that immunoglobulin family member SynCAM 1 controls number PFC was upregulated upon Combined deletion substantially lowered...
Abstract α‐Neurexins are synaptic cell‐surface molecules that required for Ca 2+ ‐triggered exocytosis. Mice lacking all three α‐neurexins show drastically reduced neurotransmitter release at excitatory and inhibitory synapses die early postnatally. Although previous histological analysis of newborn α‐neurexin triple mutants revealed only a moderate reduction in the density type II brainstem, cell culture studies proposed neurexins prominently involved synapse formation. To assess...
Two families of cell-adhesion molecules, predominantly presynaptic neurexins and postsynaptic neuroligins, are important for the formation functioning synapses in brain, mutations several genes encoding these transmembrane proteins have been found autism patients. However, very little is known about how targeted to which mechanisms regulate this process. Using various epitope-tagged primary hippocampal neurons wild-type knock-out mice vitro transgenic animals vivo , we show that trafficked...
The development of neuronal networks in the brain requires differentiation functional synapses. Neurobeachin (Nbea) was identified as a putative regulator membrane protein trafficking associated with tubulovesicular endomembranes and postsynaptic plasma membranes. Nbea is essential for evoked transmission at neuromuscular junctions, but its role central nervous system has not been characterized. Here, we have studied synapses newly generated gene-trap knockout (KO) mouse line embryonic day...
A challenge in neuroscience is to understand the mechanisms underlying synapse formation. Most excitatory synapses brain are built on spines, which actin-rich protrusions from dendrites. Spines a major substrate of plasticity, and spine pathologies observed various mental illnesses. Here we investigate role neurobeachin (Nbea), multidomain protein previously linked cases autism, synaptogenesis. We show that deletion Nbea leads reduced numbers spinous cultured neurons complete knockouts...
Significance Communication between neurons via synapses is essential for information processing and cognitive function in our brains found impaired many neuropsychiatric disorders. Synaptic transmission remarkably variable strength, cell-adhesion molecules as neurexins their binding partners are candidates to regulate neurotransmission. This study changes understanding of how neurotransmission can be adapted local demands by investigating the previously undescribed functions neurexophilins,...
Significance Paroxysmal nonkinesigenic dyskinesia (PNKD) is an autosomal dominant episodic movement disorder precipitated by coffee, alcohol, and stress. Here, we show that PNKD interacts with synaptic active zone proteins Rab3-interacting molecule (RIM)1 RIM2, localizes to synapses, modulates neurotransmitter release. knockout mice have impaired transmission short-term plasticity.
Although the CNS is immune privileged, continuous search for pathogens and tumours by cells within indispensable. Thus, distinct immune-cell populations also cross blood-brain barrier independently of inflammation/under homeostatic conditions. It was previously shown that effector memory T populate healthy parenchyma in humans and, independently, CCR5-expressing lymphocytes as well CCR5 ligands are enriched patients with multiple sclerosis. Apart from recently described CD8+ tissue-resident...
Facial nerve transection leads to functional and structural reactions in lesioned motor neurones surrounding glial cells. Data from this study provide evidence that the most rapid reaction described so far consists of an increase immunoreactivity connexin-43 (cx-43), predominant gap junction protein astrocytes. The ipsilateral facial nucleus is selectively marked as early 0.75 1.5 hours after axotomy, while unlesioned side well unoperated controls remain faintly stained. Thus, enhanced...
Neocortical astrocytes make two types of gap junctions, intercellular ones create a functional syncytium, while reflexive junctions mediate autocellular coupling and serve unknown functions (Rohlmann Wolff, 1996). Here, the question is addressed whether solitary in vitro express connexin43 (Cx43) establish absence contacts. In all media conditions tested, immunocytochemistry visualized Cx43-expression irrespective presence or Reflexive were associated with mechanical (adherent spots fascia...
VGCCs are multisubunit complexes that play a crucial role in neuronal signaling. Auxiliary α2δ subunits of modulate trafficking and biophysical properties the pore-forming α1 subunit trigger excitatory synaptogenesis. Alterations expression level were implicated several syndromes diseases, including chronic neuropathic pain, autism, epilepsy. However, contribution distinct to excitatory/inhibitory imbalance aberrant network connectivity characteristic for these pathologic conditions remains...
Neurexophilin 3 (Nxph3) is a specific ligand of synaptic α-neurexins that are essential for efficient neurotransmitter release. Previous biochemical work demonstrated Nxph3 interacts with an extracellular domain in tight complex; however, no information available on the localization or functional role brain. Here, we generated lacZ reporter gene knock-in mice to investigate distribution at single-cell level and knockout examine its importance. expression was restricted mostly...
Neurexins are key organizer molecules that regulate synaptic function and implicated in autism schizophrenia. β-neurexins interact with numerous cell adhesion receptor molecules, but their neuronal localization remains elusive. Using single-molecule tracking high-resolution microscopy to detect neurexin1β neurexin3β primary hippocampal neurons from knockin mice, we demonstrate endogenous present fewer than half of excitatory inhibitory synapses. Moreover, observe a large extrasynaptic pool...
Synapse function requires the cell-adhesion molecules neurexins (Nrxn) and neuroligins (Nlgn). Although these are essential for neurotransmission prefer distinct isoform combinations interaction, little is known about their transcriptional regulation. Here, we started to explore this important aspect because expression of Nrxn1-3 Nlgn1-3 genes altered in mice lacking regulator methyl-CpG-binding protein2 (MeCP2). Since MeCP2 can bind methylated CpG-dinucleotides Nrxn/Nlgn contain...