The ubiquitin C‐terminal hydrolase UCH‐L1 promotes bacterial invasion by altering the dynamics of the actin cytoskeleton

Invasion of eukaryotic target cells by pathogenic bacteria requires extensive remodelling of the membrane and actin cytoskeleton. Here we show that the remodelling process is regulated by the ubiquitin C‐terminal hydrolase UCH‐L1 that promotes the invasion of epithelial cells by Listeria monocytogenes and Salmonella enterica. Knockdown of UCH‐L1 reduced the uptake of both bacteria, while expression of the catalytically active enzyme promoted efficient internalization in the UCH‐L1‐negative HeLa cell line. The entry of L. monocytogenes involves binding to the receptor tyrosine kinase Met, which leads to receptor phosphorylation and ubiquitination. UCH‐L1 controls the early membrane‐associated events of this triggering cascade since knockdown was associated with altered phosphorylation of the c‐cbl docking site on Tyr1003, reduced ubiquitination of the receptor and altered activation of downstream ERK1/2‐ and AKT‐dependent signalling in response to the natural ligand Hepatocyte Growth Factor (HGF). The regulation of cytoskeleton dynamics was further confirmed by the induction of actin stress fibres in HeLa expressing the active enzyme but not the catalytic mutant UCH‐L1_C90S. These findings highlight a previously unrecognized involvement of the ubiquitin cycle in bacterial entry. UCH‐L1 is highly expressed in malignant cells that may therefore be particularly susceptible to invasion by bacteria‐based drug delivery systems.     

Preliminary clinical experience with the antiarrhythmic effect of PGF2a

A total dosage up to 1 mg PGF_2a as i.v. infusions of 10–40 μg/min. was investigated on patients with arrhythmias of several kinds. We found therapeutic effects in 5 of 6 patients with constant extrasystoles and in one patient with digitalis - induced partial AV-block respectively. In 3 of 4 patients with acute tachyarrhythmias the results were not convincing, probably due to a dosage not high enough. An increase of the diastolic stimulation threshold usually seen with other antiarrhythmics was not to be observed in 3 patients. The mechanism of action of PGF_2a has not yet been clarified.     

High resolution nuclear magnetic resonance study of base pairing in four purified transfer RNA molecules

The high resolution nuclear magnetic resonance spectra of hydrogen bonded protons in four purified tRNA molecules are reported. From the temperature and concentration dependence it is shown that these resonances arise from intramolecular hydrogen bonds.     

Enzymhistochemische Befunde im subependymalen Glialager während der Entwicklung des Rattenhirns

Zusammenfassung Die prä- bzw. postnatale enzymtopochemische Differenzierung des subependymalen Glialagers in der lateralen Wand des Vorderhornes wurde bei der SpragueDawley-Ratte untersucht. Während der pränatalen Entwicklungsphase des Rattenhirns zeichnet sich die Subependymschicht, beim Nachweis der wichtigsten hydrolytischen und oxydativen Enzyme, im allgemeinen durch eine geringe enzymatische Aktivität aus. Die Ergänzung der enzymatischen Ausstattung dieser Zellschicht erfolgt erst während der postnatalen Hirnentwicklung und zwar in den ersten 2 Lebenswochen. Eine Ausnahme von dieser Regel wurde beim Nachweis der Phosphomonoesterase-I festgestellt, welche in der prä- bzw. perinatalen Entwicklungsphase die höchste Aktivität zeigte. Die erhobenen enzymtopochemischen Befunde deuten darauf hin, daß in der subependymalen Zellschicht eine vom übrigen Hirn vor allem zeitlich abweichende topochemische Differenzierung stattfindet, welche im wesentlichen während der ersten 2 Lebenswochen abgeschlossen ist.

---

Enzyme topochemical findings of the subependymal cell layer in the developing rat brain

Summary The pre- and postnatal enzyme topochemical differentiation of the subependymal glial layer of the lateral ventricle was examined in the Sprague-Dawley rat. During the prenatal development phase of the subependymal layer, weak enzymatic activity of the most important hydrolytic and oxidative enzymes is demonstrated. The completion of the enzyme activity of this cell layer follows in the postnatal brain development period, and certainly within the first two weeks of life. An exception to this rule has been found in the case of phosphomonoesterase-I which showed the greatest activity in the pre- and perinatal development phases. The observed enzyme topochemical findings indicate that the subependymal cell layer, in contrast to other parts of the brain, shows temporally deviating topochemical differentiation, which is essentially completed in the first two weeks of life.

---

---

Mit Unterstützung durch die Deutsche Forschungsgemeinschaft (SFB 51).