Research Topics
Genomes and Genes
| T J JentschSummaryAffiliation: University of Hamburg Country: Germany Publications
| Collaborators
|
Detail Information
Publications
The CLC chloride channel familyT J Jentsch
Zentrum für Molekulare Neurobiologie, ZMNH Universität Hamburg, Martinistrasse 85, D 20246 Hamburg, Germany
Pflugers Arch 437:783-95. 1999..Their physiological relevance is obvious from three human inherited diseases (myotonia congenita, Dent's disease and Bartter's syndrome) that result from mutations in some of their members and from a knock-out mouse model...- Neuronal KCNQ potassium channels: physiology and role in diseaseT J Jentsch
Zentrum fur Molekulare Neurobiologie Hamburg, ZMNH, Hamburg University, Martinistrasse 85, D 20246 Hamburg, Germany
Nat Rev Neurosci 1:21-30. 2000..In addition, several KCNQ isoforms can associate to form heteromeric channels that underlie the M-current, an important regulator of neuronal excitability... - Functional and structural analysis of ClC-K chloride channels involved in renal diseaseS Waldegger
Zentrum für Molekulare Neurobiologie, University of Hamburg, Martinistr 85, D 20246 Hamburg, Germany
J Biol Chem 275:24527-33. 2000..Insertion of point mutations associated with Bartter's syndrome type III destroyed channel activity. We conclude that ClC-K proteins form constitutively open chloride channels with distinct physiological characteristics... - KCNQ4, a novel potassium channel expressed in sensory outer hair cells, is mutated in dominant deafnessC Kubisch
Zentrum fur Molekulare Neurobiologie Hamburg, Universitat Hamburg, Germany
Cell 96:437-46. 1999..Whereas mutations in KCNQ1 cause deafness by affecting endolymph secretion, the mechanism leading to KCNQ4-related hearing loss is intrinsic to outer hair cells... - Loss of the ClC-7 chloride channel leads to osteopetrosis in mice and manU Kornak
Zentrum fur Molekulare Neurobiologie Hamburg, ZMNH, Universitat Hamburg, D 20246, Hamburg, Germany
Cell 104:205-15. 2001..We conclude that ClC-7 provides the chloride conductance required for an efficient proton pumping by the H(+)-ATPase of the osteoclast ruffled membrane... - Barttin is a Cl- channel beta-subunit crucial for renal Cl- reabsorption and inner ear K+ secretionR Estevez
Zentrum für Molekulare Neurobiologie ZMNH, Universitat Hamburg, Falkenried 94, D 20246 Hamburg, Germany
Nature 414:558-61. 2001..This work describes the first known beta-subunit for CLC chloride channels and reveals that heteromers formed by ClC-K and barttin are crucial for renal salt reabsorption and potassium recycling in the inner ear... 
Myokymia and neonatal epilepsy caused by a mutation in the voltage sensor of the KCNQ2 K+ channelK Dedek
Zentrum für Molekulare Neurobiologie, Universitat Hamburg, D 20246 Hamburg, Germany
Proc Natl Acad Sci U S A 98:12272-7. 2001....- ClC-1 chloride channel mutations in myotonia congenita: variable penetrance of mutations shifting the voltage dependenceC Kubisch
Zentrum für Molekulare Neurobiologie Hamburg ZMNH, Universitat Hamburg, Martinistrasse 85, D 20246 Hamburg, Germany
Hum Mol Genet 7:1753-60. 1998..These complex interactions correlate clinically with various inheritance patterns, ranging from autosomal dominant with various degrees of penetrance to autosomal recessive... - KCNQ5, a novel potassium channel broadly expressed in brain, mediates M-type currentsB C Schroeder
Zentrum fur Molekulare Neurobiologie Hamburg, Hamburg University, Martinistrasse 85, D 20246 Hamburg, Germany
J Biol Chem 275:24089-95. 2000..A KCNQ5 splice variant found in skeletal muscle displays altered gating kinetics. This indicates a molecular diversity of channels yielding M-type currents and suggests a role for KCNQ5 in the regulation of neuronal excitability... - Moderate loss of function of cyclic-AMP-modulated KCNQ2/KCNQ3 K+ channels causes epilepsyB C Schroeder
Zentrum fur Molekulare Neurobiologie Hamburg, Universitat Hamburg, Germany
Nature 396:687-90. 1998..We predict that a 25% loss of heteromeric KCNQ2/KCNQ3-channel function is sufficient to cause the electrical hyperexcitability in BFNC. Drugs raising intracellular cAMP may prove beneficial in this form of epilepsy... - Multimeric structure of ClC-1 chloride channel revealed by mutations in dominant myotonia congenita (Thomsen)K Steinmeyer
Centre for Molecular Neurobiology ZMNH, Hamburg University, Germany
EMBO J 13:737-43. 1994..Analysis of both mutants shows independently that ClC-1 functions as a homooligomer with most likely four subunits... - Surface expression and single channel properties of KCNQ2/KCNQ3, M-type K+ channels involved in epilepsyM Schwake
Zentrum für Molekulare Neurobiologie Hamburg ZMNH, Universitat Hamburg, Martinistrasse 85, D 20246 Hamburg, Germany
J Biol Chem 275:13343-8. 2000..Thus, the increase in currents seen upon co-expressing KCNQ2 and KCNQ3 is predominantly due to an increase in surface expression, which is dependent on an intact carboxyl terminus... - An internalization signal in ClC-5, an endosomal Cl-channel mutated in dent's diseaseM Schwake
, Hamburg University, Falkenried 94, D-20246 Hamburg, Germany
J Biol Chem 276:12049-54. 2001..Thus, the endocytosis of ClC-5, which itself is crucial for the endocytosis of other proteins, depends on the interaction of a carboxyl-terminal internalization signal with ubiquitin-protein ligases containing WW domains... - A constitutively open potassium channel formed by KCNQ1 and KCNE3B C Schroeder
Zentrum fur Molekulare Neurobiologie Hamburg, Hamburg University, Germany
Nature 403:196-9. 2000.... - Kidney-specific upregulation of vitamin D3 target genes in ClC-5 KO miceT Maritzen
Zentrum fur Molekulare Neurobiologie Hamburg, ZMNH, Universitat Hamburg, Hamburg, Germany
Kidney Int 70:79-87. 2006..The activation of genes in distal nephron segments by hormones that are normally endocytosed in the proximal tubule may extend to other pathways like those activated by retinoic acid... - Male germ cells and photoreceptors, both dependent on close cell-cell interactions, degenerate upon ClC-2 Cl(-) channel disruptionM R Bösl
Zentrum für Molekulare Neurobiologie Hamburg ZMNH, Universitat Hamburg, Martinistrasse 52, D 20246 Hamburg, Germany
EMBO J 20:1289-99. 2001..Thus, ClC-2 disruption entails the death of two cell types which depend on supporting cells that form the blood-testes and blood-retina barriers. We propose that ClC-2 is crucial for controlling the ionic environment of these cells... - Disruption of KCC2 reveals an essential role of K-Cl cotransport already in early synaptic inhibitionC A Hübner
Zentrum fur Molekulare Neurobiologie Hamburg, ZMNH, Universitat Hamburg, Martinistr 52, D 20246, Hamburg, Germany
Neuron 30:515-24. 2001..Patch-clamp measurements of embryonic day 18.5 spinal cord motoneurons demonstrated an excitatory GABA and glycine action in the absence, but not in the presence, of KCC2, revealing a crucial role of KCC2 for synaptic inhibition... - Mutations in dominant human myotonia congenita drastically alter the voltage dependence of the CIC-1 chloride channelM Pusch
Center for Molecular Neurobiology ZMNH, Hamburg University, Germany
Neuron 15:1455-63. 1995..Remarkably, a human mutation affecting an adjacent residue (E291K) is fully recessive. Large shifts in the voltage dependence of gating may be common to many mutations in dominant myotonia congenita... - Pathophysiological mechanisms of dominant and recessive KVLQT1 K+ channel mutations found in inherited cardiac arrhythmiasB Wollnik
Centre for Molecular Neurobiology ZMNH, Hamburg University, Germany
Hum Mol Genet 6:1943-9. 1997..This fully explains the different patterns of inheritance. Further, we identified a novel splice variant of the KVLQT1 gene, but could not achieve functional expression of this nor of a previously described heart-specific isoform... - KCNQ4, a K+ channel mutated in a form of dominant deafness, is expressed in the inner ear and the central auditory pathwayT Kharkovets
Zentrum fur Molekulare Neurobiologie Hamburg, Universitat Hamburg, Martinistrasse 85, D 20246 Hamburg, Germany
Proc Natl Acad Sci U S A 97:4333-8. 2000..This is the first ion channel shown to be specifically expressed in a sensory pathway. Moreover, the expression pattern of KCNQ4 in the mouse auditory system raises the possibility of a central component in the DFNA2 hearing loss... - Temperature dependence of fast and slow gating relaxations of ClC-0 chloride channelsM Pusch
Center for Molecular Neurobiology ZMNH, Hamburg University, Germany
J Gen Physiol 109:105-16. 1997.... - Mutations in the a3 subunit of the vacuolar H(+)-ATPase cause infantile malignant osteopetrosisU Kornak
Zentrum fur Molekulare Neurobiologie Hamburg, Universitat Hamburg, Germany
Hum Mol Genet 9:2059-63. 2000..Our work shows that mutations in the gene encoding the a3 subunit of the proton pump are a rather common cause of infantile osteopetrosis and suggests that this disease is genetically heterogeneous... - Molecular physiology of renal chloride channelsK Steinmeyer
Center for Molecular Neurobiology ZMNH, Hamburg University, Germany
Curr Opin Nephrol Hypertens 7:497-502. 1998..This review will focus on cloned chloride channels expressed in renal cells... - A family of putative chloride channels from Arabidopsis and functional complementation of a yeast strain with a CLC gene disruptionM Hechenberger
Center for Molecular Neurobiology ZMNH, Hamburg University, Martinistr 52, D 20246 Hamburg, Germany
J Biol Chem 271:33632-8. 1996..This suggests that in Arabidopsis AtCLC-d functions as an intracellular chloride channel... - Pores formed by single subunits in mixed dimers of different CLC chloride channelsF Weinreich
, ZMNH, Hamburg University, Martinistrasse 85, D-20246 Hamburg, Germany
J Biol Chem 276:2347-53. 2001..We conclude that each monomer individually forms a gated pore. CLC dimers in general must be imagined as having two pores, as shown previously for ClC-0... - ClC-5 Cl- -channel disruption impairs endocytosis in a mouse model for Dent's diseaseN Piwon
Zentrum fur Molekulare Neurobiologie Hamburg, Universitat Hamburg, Germany
Nature 408:369-73. 2000..The balance between these opposing effects, both of which are secondary to the defect in proximal tubular endocytosis, probably determines whether there will be hypercalciuria and kidney stones... - Golgi localization and functionally important domains in the NH2 and COOH terminus of the yeast CLC putative chloride channel Gef1pB Schwappach
Zentrum für Molekulare Neurobiologie Hamburg ZMNH, Hamburg University, Martinistrasse 52, D 20246 Hamburg, Germany
J Biol Chem 273:15110-8. 1998..The second CBS domain can be transplanted to the amino terminus without loss of function, but could not be replaced by the corresponding domain of the homologous mammalian channel ClC-2... - ClC-5, the chloride channel mutated in Dent's disease, colocalizes with the proton pump in endocytotically active kidney cellsW Gunther
Zentrum für Molekulare Neurobiologie Hamburg ZMNH, Universitat Hamburg, Martinistrasse 85, D 20246 Hamburg, Germany
Proc Natl Acad Sci U S A 95:8075-80. 1998.... - From tonus to tonicity: physiology of CLC chloride channelsS Waldegger
Center for Molecular Neurobiology ZMNH, University of Hamburg, Germany
J Am Soc Nephrol 11:1331-9. 2000..These diseases, together with the diabetes insipidus symptoms of a knockout mouse model, emphasize the physiologic relevance of this ion channel family... - Two highly homologous members of the ClC chloride channel family in both rat and human kidneyS Kieferle
Centre for Molecular Neurobiology ZMNH, Hamburg University, Germany
Proc Natl Acad Sci U S A 91:6943-7. 1994..Glycosylation occurs between domains D8 and D9, leading to a revision of the transmembrane topology model for ClC channels... - ClC-6 and ClC-7 are two novel broadly expressed members of the CLC chloride channel familyS Brandt
Center for Molecular Neurobiology Hamburg, ZMNH, Hamburg University, Germany
FEBS Lett 377:15-20. 1995..Hydropathy analysis indicates that domain D4 cannot serve as a transmembrane domain. Both ClC-6 and ClC-7 cannot be expressed as chloride channels in Xenopus oocytes, either singly or in combination... - Disruption of ClC-3, a chloride channel expressed on synaptic vesicles, leads to a loss of the hippocampusS M Stobrawa
Zentrum fur Molekulare Neurobiologie Hamburg, Universitat Hamburg, Martinistrasse 85, D 20246, Hamburg, Germany
Neuron 29:185-96. 2001..Mice almost lacking the hippocampus survive and show several behavioral abnormalities but are still able to acquire motor skills... - Primary structure and functional expression of a developmentally regulated skeletal muscle chloride channelK Steinmeyer
Centre for Molecular Neurobiology ZMNH, Hamburg University, Germany
Nature 354:301-4. 1991..This and the functional destruction of this channel in mouse myotonia suggests that we have cloned the major skeletal muscle chloride channel... - Inactivation of muscle chloride channel by transposon insertion in myotonic miceK Steinmeyer
Centre for Molecular Neurobiology ZMNH, Hamburg University, Germany
Nature 354:304-8. 1991..Together with the lack of recombination between the Clc-1 gene and the adr locus, this strongly suggests a lack of functional chloride channels as the primary cause of mouse myotonia... - Genomic organization of the human muscle chloride channel CIC-1 and analysis of novel mutations leading to Becker-type myotoniaC Lorenz
Center for Molecular Neurobiology ZMNH, Hamburg University, Germany
Hum Mol Genet 3:941-6. 1994..Functional expression of R496S cRNA in Xenopus oocytes did not yield detectable currents. It neither suppressed wild-type currents in a co-expression assay, confirming it as a recessive mutation... - A chloride channel widely expressed in epithelial and non-epithelial cellsA Thiemann
Centre for Molecular Neurobiology ZMNH, Hamburg University, Hamburg, Germany
Nature 356:57-60. 1992..The presence of ClC-2 in such different cell types contrasts with the highly specialized expression of ClC-1 (ref. 9) and also with the cloned cation channels, and suggests that its function is important for most cells... - Properties of voltage-gated chloride channels of the ClC gene familyT J Jentsch
Centre for Molecular Neurobiology Hamburg ZMNH, Hamburg University, Germany
J Physiol 482:19S-25S. 1995..Functional characterization is most advanced with ClC-0, ClC-1 (mutations which cause myotonia) and ClC-2, a swelling-activated chloride channel. Many of the new ClC family members cannot yet be expressed functionally...