Lipid Binding Defects and Perturbed Synaptogenic Activity of a Collybistin R290H Mutant That Causes Epilepsy and Intellectual Disability

Signaling at nerve cell synapses is a key determinant of proper brain function, and synaptic defects—or synaptopathies—are at the basis of many neurological and psychiatric disorders. In key areas of the mammalian brain, such as the hippocampus or the basolateral amygdala, the clustering of the scaffolding protein Gephyrin and of γ-aminobutyric acid type A receptors at inhibitory neuronal synapses is critically dependent upon the brain-specific guanine nucleotide exchange factor Collybistin (Cb). Accordingly, it was discovered recently that an R290H missense mutation in the diffuse B-cell lymphoma homology domain of Cb, which carries the guanine nucleotide exchange factor activity, leads to epilepsy and intellectual disability in human patients. In the present study, we determined the mechanism by which the Cb^R290H mutation perturbs inhibitory synapse formation and causes brain dysfunction. Based on a combination of biochemical, cell biological, and molecular dynamics simulation approaches, we demonstrate that the R290H mutation alters the strength of intramolecular interactions between the diffuse B-cell lymphoma homology domain and the pleckstrin homology domain of Cb. This defect reduces the phosphatidylinositol 3-phosphate binding affinity of Cb, which limits its normal synaptogenic activity. Our data indicate that impairment of the membrane lipid binding activity of Cb and a consequent defect in inhibitory synapse maturation represent a likely molecular pathomechanism of epilepsy and mental retardation in humans.     

ARDRA and RAPD-fingerprinting reject the sibling species concept for the ciliate Paramecium caudatum (Ciliophora, Protoctista)

Morphologically indistinguishable sibling species also known as syngens are a characteristic taxonomic feature of the ciliate genus Paramecium . This has been convincingly demonstrated for the P. aurelia species complex. For a long time this feature has also been assumed for P. caudatum . Classical morphology based techniques of taxonomic analysis are often inefficient to study sibling specie. We therefore investigated 14 P. caudatum strains of seven supposedly different syngens using random amplified polymorphic DNA (RAPD)-fingerprinting and amplified ribosomal DNA restriction analyses (ARDRA, Riboprinting). The RAPD patterns revealed by five different random primers were similar between the different strains of the same syngen (similarity index ranging from 73 to 91%) and also between strains of supposedly different syngens (similarity index ranging from 67 to 91%). The amplified 18S rRNA-fragments of supposedly different syngens, as well as the restriction patterns of these fragments digested by five different endonucleases, were identical for all investigated P. caudatum stains. Consequently we reject the sibling species hypothesis for P. caudatum . According to our molecular analysis, P. caudatum is not a species complex, but just one single species.     

Inactivation of glutamine synthetase by adenylylation in intact cells of E. coli

Summary The adenine pool of a purineless mutant of E. coli was radioactively labelled by short incubation with ¹⁴C-adenine.The glutamine synthetase was inactivated in vivo by incubation of the cell suspension with 2x10^-3 M NH₄ ⁺ for 2 min. The inactivated glutamine synthetase was extracted from the cells and purified 20-fold.Incubation of the purified glutamine synthetase with phosphodiesterase regenerated the biosynthetic activity of the enzyme paralleled by the liberation of ¹⁴C-adenine and ¹⁴C-adenosine. ¹⁴C-adenine and ¹⁴C-adenosine were also obtained when inactivated glutamine synthetase, prepared in vitro by use of ¹⁴C-ATP and purified adenylylating enzyme, was incubated with phosphodiesterase under the same conditions.The similar liberation of adenine derivatives by phosphodiesterase from glutamine synthetase inactivated in a cell-free system as well as in intact cells, demonstrates that in both cases the inactivation consists in an adenylylation of the enzyme.     

Unterschiede im revier- und sexualverhalten endemisch-anatolischer zahnkarpfen (pisces,cyprinodontidae)

The endemic Anatolian cyprinodonts Aphanius chantrei, A. (Kosswigichtys) asquamatus, and A. anatoliae show definite interspecific differences in their territorial and sexual behaviour under laboratory conditions. Intraspecific differences were found in the nine populations of A. anatoliae investigated.A. chantrei and Kosswigichthys show almost the same territorial behaviour. In A. anatoliae territoriality is found in three populations; the remaining six populations show no territoriality.The sexual behaviour consists of visual display elements and of elements which enable the fish to keep close contact without actually touching each other. The sequence of elements can be variable. Only two populations of A. anatoliae have retained display elements; the remaining seven populations have lost all of them.A correlation is discussed between biotope conditions and sexual behaviour. Display and territorial behaviour may have become superfluous in extreme, sulphate-containing habitats, where a lack of flora has led to a lack of spawning sites. Under changing breeding conditions the newly evolved element with fish staying close together (male underneath the female) may have replaced the former display elements.     

Ein einfaches Mikrokolorimeter

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Book reviews

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Book reviews

     

Ro?haarpilze als Nestbau-Material brasilianischer V?gel

Zusammenfassung In Brasilien verwenden einige Vogelarten die roßhaarähnlichen Rhizomorphen der PilzgattungMarasmius zum Nestbau. Dieses Material, das nicht mit verwitterten Ranken der BromelieTillandsia usneoides verwechselt werden darf, ist ebenso zur Auspolsterung der Nestmulde in offenen Napfnestern (Roßhaarkissen!) wie als Binde- und Flechtmaterial zum Befestigen von Nestern im Gezweig und zur Herstellung von geschlossenen Beutelnestern dienlich. Die weite Verbreitung vonMarasmius pilzen mit Roßhaarmyzelien macht die Verwendung dieser Fäden als Baumaterial in Vogelnestern auch in anderen tropischen Gebieten der Erde wahrscheinlich. Anhangweise wird ein Niststoff behandelt, der aus pilzüberzogenen Reisern besteht. Dieses Material wirkt anscheinend durch seine kalkweiße Farbe anziehend auf manche Vogelarten.Mit 4 Abbildungen