PubMed Health⌕ Search

Biomedical subjects

M Kübler

Publications and source records attributed to M Kübler.

11 recordsLinked to original sources
PubMed1998

Identification of a novel Ran binding protein 2 related gene (RANBP2L1) and detection of a gene cluster on human chromosome 2q11-q12.

The giant 358-kDa protein Ran binding protein 2 (RanBP2/Nup358) is localized at the cytoplasmic side of the nuclear pore complex and likely constitutes the Ran-GTP binding site at the cytoplasmic face of the complex. RanBP2/Nup358 furthermore acts as a chaperone for red/green opsin molecules. Here, we report on the physical mapping of human RanBP2 between markers D2S340 and D2S1893. A duplication of the 5'-end sequence of RanBP2 occurs within 3 Mb distal to RanBP2. Detailed sequence analysis resulted in primers specific for this distal duplication. Polymerase chain reaction-based screening of cDNA libraries indicates that this transcript, called RanBP2alpha (HGMW-approved symbol RANBP2L1), is expressed in several tissues. Screening of a fetal brain cDNA library yielded a 4057-bp partial cDNA clone for RanBP2alpha. Its 5'-end is almost identical to RanBP2, whereas its 3'-part is distinct from RanBP2. Northern blot analysis using a probe of the 3'-untranslated sequence of RanBP2alpha detected in several tissues an 8-kb transcript representing the full length of the transcript. In pancreas and placenta, an additional transcript of 14 kb was detected. PAC clones containing the bona fide RanBP2 sequences were localized to 2q11-q12 by FISH analysis, and a region of high similarity was detected on 2p11-p12. In summary, we have identified a RanBP2 gene cluster on 2q11-q12 together with a novel gene termed RanBP2alpha, with high sequence similarity to RanBP2.

Amino Acid Sequence↗
PubMed1998

Construction of a gene map of the nephronophthisis type 1 (NPHP1) region on human chromosome 2q12-q13.

A gene for the autosomal recessive kidney disorder juvenile nephronophthisis (NPH) is located on chromosome 2q between markers D2S1893 and D2S1888. Recently, the presence of large homozygous deletions was described in the majority of NPH patients. We constructed an integrated YAC/PAC contig of 54 markers and 30 PAC clones that encompasses this deletion and the flanking inverted duplication. Thirty-six novel sequence-tagged site markers were generated for this region of 2-3 Mb, 22 of which represent PAC ends. Ten of 18 multiplex NPH families show a homozygous deletion for 8 consecutive markers. BlastN database search and expressed sequence tag (EST) mapping led to the localization of 18 EST clones to the integrated contig, representing 11 putative transcribed sequences. Seven EST clones were localized to the NPHP1 region between D2S1893 and D2S1888. Two EST clones, zc07a11 from a human parathyroid tumor library and yy63e10 from a multiple sclerosis lesion library, are located in the deletion region. PCR amplification experiments indicate that zc07a11 represents a chimeric cDNA. Through FISH analysis the NPHP1 deletion region was localized to 2q12-q13. In summary, our study provides a high-resolution physical map of the NPHP1 region with 7 precisely localized expressed sequences, 2 of which have recently been shown to be part of a gene for NPH. These data will alleviate the identification of further genes of a homozygous gene deletion syndrome in patients with NPH and oculomotor apraxia and will be instrumental in the characterization of the molecular mechanism leading to the large homozygous deletion in this region. The data furthermore provide an important step toward the construction of a sequence-ready PAC contig of this region.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Molecular cloning of the interleukin-1 gene cluster: construction of an integrated YAC/PAC contig and a partial transcriptional map in the region of chromosome 2q13.

Genes of the interleukin-1 (IL-1) gene cluster localized on chromosome 2q13 are implicated in many physiological and pathophysiological processes. We present here a high-resolution physical map of this region between markers D2S2008 and D2S4/PAX8. An integrated YAC/PAC contig and a partial transcriptional map were constructed by STS-constent mapping using the CEPH YAC library and three PAC libraries. A total of 3 YACs, 34 PACs, and 56 STSs were integrated: 33 newly generated probes to PAC end sequences, 9 polymorphic and 4 nonpolymorphic markers, 5 known genes, 4 expressed sequence tags, and 1 pseudogene. Within the map, a complete PAC contig of > 1 Mb encompasses the IL-1 gene cluster and PAX8, a paired-box-containing gene. This allowed us to define the transcriptional orientation of GLVR1, IL1B, and IL1RN and to show that PAX8 is localized outside the IL-1 gene cluster. FISH analysis localized PAC clones containing the IL-1 gene cluster to 2q12-q13. The data provide the basis for further characterization of the IL-1 gene cluster and for the construction of a sequence-ready PAC contig of this region.

Base Sequence↗
PubMed1975

Kinetics of inactivation and recovery of the slow inward current in the mammalian ventricular myocardium.

In order to study the kinetics of inactivation and recovery of the slow inward current in the mammalian ventricular myocardium voltage clamp experiments using the double sucrose gap technique were performed on isolated trabeculae and papillary muscles of cats. The separation of the slow inward current from the fast Na current was achieved by use of the conditioning clamp procedure. 1. The decay of the Ca current reflects the inactivation which develops due to depolarization. The rate of inactivation depends upon the membrane potential. Excess Ca (8.8 mM) accelerates the inactivation speed indicating that Ca ions not only act as charge carrier of the slow inward current but might influence in addition the kinetics of the slow membrane channel. In the presence of a lowered temperature a deceleration of inactivation (Q10 2.3) occurs. 2 If the membrane is repolarized a recovery process takes place restoring the availability of the slow membrane channel. As the inactivation the recovery rate depends upon the membrane potential. Excess Ca causes an acceleration whereas a decrease in temperature diminishes the recovery speed (Q10 2.3). Consequently, the Ca supply to the myocardial cell can be modified not only by changes of the transmembrane Ca concentration gradient or by an alteration of the Ca conductance of the slow channel but also by changes in the degree of recovery after a preceding Ca current. 3. Compared with the inactivation the recovery proceeds very slowly. Assuming that this slow recovery represents an inherent kinetic feature of the slow channel the kinetics of inactivation and removal of inactivation are not describable by a single inactivation variable (called as f by Reuter, 1973) which is of the Hodgkin-Huxley type. If a second inactivation variable (called as l) would be introduced additionally a formulation of the inactivation-recovery process of the slow membrane channel on the basis of the Hodgkin-Huxley model becomes feasible.

Action Potentials↗
PubMed1975

The influence of metabolic inhibitors upon the transmembrane slow inward current in the mammalian ventricular myocardium.

The effect of metabolic alterations of isolated trabeculae and papillary muscles of cats upon the transmembrane slow inward current was studied in voltage clamp experiments using the double sucrose gap technique. The slow inward current which is mainly carried by Ca ions was separated from the fast Na current by applying the conditioning clamp technique. 1. After inhibition of the oxidative phosphorylation of the myocardial cell caused by cyanide (100 mg/l), the transmembrane slow inward current decreased by 25% on average within 25 min. The same diminution appeared after poisoning with 2.4 dinitrophenol (40 mg/l) which amounted to 46% on an average. In both cases the extrapolated reversal potential of the slow inward current was shifted to less positive values. The reduction of the slow inward current seems to reflect a diminished Ca driving force due to a metabolically evoked increase in intracellular free Ca. But these metabolic inhibitors might exert some direct effects upon the membrane since after the treatment with cyanide and 2.4 dinitrophenol, respectively, a slight delay of current inactivation could be observed. Nevertheless, the kinetics of the recovery from inactivation remained unaffected. 2. Metabolic poisoning abolished the normal response of the slow inward current to an increase of the extracellular Ca concentration or to the addition of Sr ions. Excess Ca failed to augment the current, and in some cases even a slight diminution occurred. If at all 5.5 mM Sr caused an increase by not more than 20%. These unusual reactions may also result from a reduced driving force for Ca or Sr, respectively. 3. Catecholamines still exerted their promoting effects upon the slow inward current after poisoning with cyanide or 2,4 dinitrophenol. The addition of 5 mg/l isoproterenol not only neutralized the effect of these metabolic inhibitors but caused an increase of the slow inward current even surpassing the initial control values.

Animals↗