A5079702745- Ion channel regulation and function
- Cardiac electrophysiology and arrhythmias
- Neuroscience and Neuropharmacology Research
- Neurobiology and Insect Physiology Research
- Nicotinic Acetylcholine Receptors Study
- Ion Transport and Channel Regulation
- Biochemical and Molecular Research
- Insect and Arachnid Ecology and Behavior
- Insect Utilization and Effects
- Acute Lymphoblastic Leukemia research
- Polyamine Metabolism and Applications
- Cardiac Ischemia and Reperfusion
- Ion Channels and Receptors
- Neuroscience and Neural Engineering
- RNA and protein synthesis mechanisms
- Insect and Pesticide Research
- Cannabis and Cannabinoid Research
- Insects and Parasite Interactions
- Neurotransmitter Receptor Influence on Behavior
- Amino Acid Enzymes and Metabolism
- Antimicrobial Peptides and Activities
- Bacteriophages and microbial interactions
- Neuroscience of respiration and sleep
- DNA and Nucleic Acid Chemistry
- Invertebrate Immune Response Mechanisms
Paracelsus Medizinische Privatuniversität
2022-2025
Charité - Universitätsmedizin Berlin
2008-2024
Freie Universität Berlin
2023
Humboldt-Universität zu Berlin
2005-2023
University of Cologne
2014-2017
Philipps University of Marburg
1996-2008
Saxon Academy of Sciences and Humanities in Leipzig
2003-2005
University of Freiburg
2002-2003
Czech Academy of Sciences, Institute of Physiology
2002
Max Planck Institute for Biophysical Chemistry
1998-2001
Glutamatergic inputs to the ventral tegmental area (VTA), thought crucial capacity of VTA detect and signal stimulus salience, have been reported arise in but a few structures. However, afferent system comprises very abundant neurons within large formation extending from prefrontal cortex caudal brainstem. Neurons nearly all parts this continuum may be glutamatergic equivalently important function. Thus, we sought identify full range by combining retrograde transport wheat germ...
Abstract The bed bug, Cimex lectularius , has re-established itself as a ubiquitous human ectoparasite throughout much of the world during past two decades. This global resurgence is likely linked to increased international travel and commerce in addition widespread insecticide resistance. Analyses C. sequenced genome (650 Mb) 14,220 predicted protein-coding genes provide comprehensive representation that are traumatic insemination, reduced chemosensory repertoire related obligate...
Tandem pore domain acid-sensitive K<sup>+</sup> channel 3 (TASK-3) is a new member of the tandem potassium family. A cDNA encoding 365- amino acid polypeptide with four putative transmembrane segments and two regions was isolated from guinea pig brain. An orthologous sequence cloned human genomic library. Although TASK-3 62% identical to TASK-1, cytosolic C-terminal only weakly conserved. Analysis gene structure identified an intron within conserved GYG motif first region. Reverse...
We have isolated KCNQ5, a novel human member of the KCNQ potassium channel gene family that is differentially expressed in subregions brain and skeletal muscle. When in<i>Xenopus</i> oocytes, KCNQ5 generated voltage-dependent, slowly activating K<sup>+</sup>-selective currents displayed marked inward rectification at positive membrane voltages. were insensitive to K<sup>+</sup> blocker tetraethylammonium but strongly inhibited by selective M-current linopirdine. Upon coexpression with...
Andersen's syndrome, an autosomal dominant disorder related to mutations of the potassium channel Kir2.1, is characterized by cardiac arrhythmias, periodic paralysis, and dysmorphic bone structure. The aim our study was find out whether heteromerization Kir2.1 channels with wild-type Kir2.2 Kir2.3 contributes phenotype syndrome. following results show that Kir2.x can form functional heteromers: ( i ) HEK293 cells transfected Kir2.x–Kir2.y concatemers expressed inwardly rectifying K + a...
Two cDNAs encoding novel K+channels, THIK-1 and THIK-2 (tandem pore domainhalothane inhibited K+channel), were isolated from rat brain. The proteins of 405 430 amino acids 58% identical to each other. Homology analysis showed that the channels form a separate subfamily among tandem domain K+ channels. genes human orthologs identified as genomic data base entries. They possess one intron assigned chromosomal region 14q24.1–14q24.3 (human (h) THIK-1) 2p22–2p21 (hTHIK-2). In (r), (rTHIK-1) is...
The large chlorella virus PBCV-1, which contains double-stranded DNA (dsDNA), encodes a 94-codon open reading frame (ORF) that motif resembling the signature sequence of pore domain potassium channel proteins. Phylogenetic analyses encoded protein, Kcv, indicate previously unidentified type channel. messenger RNA by ORF leads to functional expression potassium-selective conductance in Xenopus laevis oocytes. blockers amantadine and barium, but not cesium, inhibit this conductance, addition...
Cochlear inner hair cells (IHCs) transduce sound-induced vibrations into a receptor potential (RP) that controls afferent synaptic activity and, consequently, frequency and timing of action potentials in the postsynaptic auditory neurons. The RP is thought to be shaped by two voltage-dependent K+ conductances, I(K,f) I(K,s), are carried large-conductance Ca2+- (BK)- K(V)-type channels. Using whole-cell voltage-clamp recordings acutely isolated mouse cochlea, we show IHCs display an...
Abstract The use of Escherichia coli asparaginase II as a drug for the treatment acute lymphoblastic leukemia is complicated by significant glutaminase side activity enzyme. To develop enzyme forms with reduced activity, number variants amino acid replacements in vicinity substrate binding site were constructed and assayed their kinetic stability properties. We found that A sp248 affected glutamine turnover much more strongly than asparagine hydrolysis. In wild‐type enzyme, N248 modulates to...
1 The aim of the study was to compare properties cloned Kir2 channels with native rectifier in guinea-pig (gp) cardiac muscle. cDNAs gpKir2.1, gpKir2.2, gpKir2.3 and gpKir2.4 were obtained by screening a cDNA library from ventricle. 2 A partial genomic structure all gpKir2 genes deduced comparison nucleotide sequences derived library. 3 cell-specific expression channel subunits studied isolated cardiomyocytes using multi-cell RT-PCR approach. It found that gpKir2.2 gpKir2.3, but not...
The two‐pore‐domain potassium channels TASK‐1, TASK‐3 and TASK‐5 possess a conserved C‐terminal motif of five amino acids. Truncation the C‐terminus TASK‐1 strongly reduced currents measured after heterologous expression in Xenopus oocytes or HEK293 cells decreased surface membrane GFP‐tagged channel proteins. Two‐hybrid analysis showed that domain TASK‐5, but not TASK‐4, interacts with isoforms adapter protein 14‐3‐3. A pentapeptide at extreme RRx(S/T)x, was found to be sufficient for weak...
Rat and human cDNAs were isolated that both encoded a 360 amino acid polypeptide with tertiary structure typical of inwardly rectifying K + channel (Kir) subunits. The new proteins, termed Kir7.1, <37% identical to other Kir subunits showed various unique residues at conserved sites, particularly near the pore region. High levels Kir7.1 transcripts detected in rat brain, lung, kidney, testis. In situ hybridization brain sections demonstrated mRNA was absent from neurons glia but strongly...
Inward-rectifier K(+) channels of the ROMK (K(ir)1.1) subtype are responsible for secretion and control NaCl absorption in kidney. A hallmark these is their gating by intracellular pH neutral range. Here we show that a lysine residue close to TM1, identified previously as structural element required pH-induced gating, protonated at this protonation drives other K(ir) channels. Such anomalous titration (Lys-80 K(ir)1.1) accomplished tertiary structure protein: two arginines distant N C...
The amino acid sequence and tertiary structure of Wolinella succinogenes l ‐asparaginase were determined, compared with the structures other type‐II bacterial ‐asparaginases. Each chain this homotetrameric enzyme consists 330 residues. is 40–50% identical to sequences related proteins from sources, all residues previously shown be crucial for catalytic action these enzymes are identical. Differences between W that discussed in terms possible influence on substrate specificity. overall fold...
Members of the Kir2 subfamily inwardly rectifying K + channels characterized by their strong current rectification are widely expressed both in periphery and CNS mammals. We have cloned from rat brain a fourth member, designated Kir2.4 (IRK4), which shares 53–63% similarity to Kir2.1, Kir2.2, or Kir2.3 on amino acid level. In situ hybridization analysis identifies as most restricted all Kir subunits brain. transcripts predominantly motoneurons cranial nerve motor nuclei within general...
Two novel alternatively spliced isoforms of the human two‐pore‐domain potassium channel TREK‐2 were isolated from cDNA libraries kidney and fetal brain. The cDNAs 2438 base pairs (bp) (TREK‐2b) 2559 bp (TREK‐2c) encode proteins 508 amino acids each. RT‐PCR showed that TREK‐2b is strongly expressed in (primarily proximal tubule) pancreas, whereas TREK‐2c abundantly In situ hybridization revealed a very distinct expression pattern rat brain which partially overlapped with TREK‐1. Expression...
Background: Neuropeptides are key players in information transfer and act as important regulators of development, growth, metabolism, reproduction within multi-cellular animal organisms (Metazoa).These short protein-like substances show a high degree structural variability recognized the most diverse group messenger molecules.We used transcriptome sequences from 1KITE (1K Insect Transcriptome Evolution) project to search for neuropeptide coding 24 species non-pterygote hexapod lineages...
Somatic mutations are common in cancer, with only a few driving the progression of disease, while most silent passengers. Some may hinder or even reverse cancer progression. The voltage-gated proton channel (HV1) plays key role cellular pH homeostasis and shows increased expression several malignancies. Inhibiting HV1 cells reduces invasion, migration, extrusion, recovery, impacting tumor Focusing on HVCN1, gene coding for human (hHV1), 197 were identified from three databases: 134 missense...
Escherichia coli asparaginase II catalyzes the hydrolysis of l ‐asparagine to ‐aspartate via a threonine‐bound acylenzyme intermediate. A nearly inactive mutant in which one active site threomines, Thr‐89, was replaced by valine constructed, expressed, and crystallized. Its structure, solved at 2.2 Å resolution, shows high overall similarity wild‐type enzyme, but an aspartyl moiety is covalently bound Thr‐12, resembling reaction Kinetic analysis confirms deacylation deficiency, also...
Adipokinetic hormone (AKH) peptides in insects serve the endocrine control of energy supply. They also produce, however, neuronal, vegetative, and motor effects, suggesting that AKHs orchestrate adaptive behavior by multiple actions. We have cloned, for Periplaneta americana, AKH receptor to determine its localization and, based on current measurements neurons heterologous expression systems, mechanisms Apart from fat body, various express receptor, among them abdominal dorsal unpaired...
Recently mutations in the LGI1 (leucine‐rich, glioma‐inactivated 1) gene have been found human temporal lobe epilepsy. We now identified three formerly unknown LGI‐like genes. Hydropathy plots and pattern analysis showed that LGI genes encode proteins with large extra‐ intracellular domains connected by a single transmembrane region. Sequence demonstrated LGI1, LGI2, LGI3, LGI4 form distinct subfamily when compared to other leucine‐rich repeat‐containing proteins. In silico mapping radiation...
Abstract Tandem‐pore domain (2P‐domain) K + ‐channels regulate neuronal excitability, but their function in glia, particularly, retinal glial cells, is unclear. We have previously demonstrated the immunocytochemical localization of 2P‐domain channels TASK‐1 and TASK‐2 Müller cells amphibians. The purpose present study was to determine whether these were functional, by employing whole‐cell recording from frog mammalian (guinea pig, rat mouse) confocal microscopy monitor swelling cells....