Potassium conductances in hippocampal neurons blocked by excitatory amino-acid transmitters

Excitatory amino acids mediate fast synaptic transmission in the central nervous system through the activation of at least three distinct ionotropic receptors: N-methyl-D-aspartate (NMDA), the alpha-amino-3-hydroxy-5-methyl-isoxasole-4-propionate (AMPA)/quisqualate (QUIS) and the kainate subtypes (for reviews, see refs 1, 2). They also activate the additional QUIS 'metabotropic' receptor (sensitive to trans-1-amino-cyclopentyl-1,3-dicarboxylate, ACPD) linked to inositol phospholipid metabolism. We have used hippocampal slice cultures to study the electrophysiological consequences of the metabotropic response. We find that activation of an ACPD-sensitive QUIS receptor produces a 'slow' excitation of CA3 pyramidal cells, resulting from depression of a Ca2(+)-dependent K+ current and a voltage-gated K+ current. Combined voltage-clamp and microfluorometric recordings show that, although these receptors can trigger an increase in intracellular Ca2+ concentration, suppression of K+ currents is independent of changes in intracellular Ca2+. These effects closely resemble those induced by activating muscarinic acetylcholine receptors in the same neurons and suggest that excitatory amino acids not only act as fast ionotropic transmitters but also as slow neuromodulatory transmitters.     

IgG purification to measure the level of an iodinated thyroglobulin peptide, the 3,5,3',5' tetraiodo-l-tyrosyl-l-tyrosine in human serum

Antibodies reacting with 3,5,3',5' tetraiodo-l-tyrosyl-l-tyrosine (I2Tyr-I2Tyr) were elicited in rabbits by immunization with an oxidized yeast conjugate coupled with I2Tyr-I2Tyr. Ion-exchange chromatography was used to purify immunoglobulins, in order to improve the specificity in measurement of I2Tyr-I2Tyr level in patient serum. IgG binding capacity versus I2Tyr-I2Tyr was considerably increased after immunoglobulin purification.     

Injection of a soluble sperm fraction into sea-urchin eggs triggers the cortical reaction

Fertilization membranes form around unfertilized sea-urchin eggs after microinjection of a soluble spermatozoa fraction isosmotic with seawater. This demonstrates that the spermatozoon contains a chemical that triggers an increase in cytosolic calcium, leading to exocytosis of cortical granules. It also demonstrates that the triggering mechanism does not require an externally-activated egg-membrane process. Further experiments show that the chemical trigger is not calcium.     

Communicating junctions between pillar cells in the gills of the atlantic hagfish,Myxine glutinosa

Summary In the respiratory lamellae of the gills of the atlantic hagfish,Myxine glutinosa, pillar cells are coupled by communicating junctions. It is suggested that these cells behave like a functional syncytium.Supported by the DFG, SFB 146. The authors are indebted to Drs F. Walvig and H. Stolte for kindly providing the hagfish. The expert technical assistance of G. Voss-Wermbter, Dipl.-Ing., and H. Heidrich is gratefully acknowledged.     

Aggregates of acetylcholinesterase induced by acetylcholine receptor-aggregating factor

Basal lamina-rich extracts of Torpedo californica electric organ contain a factor that causes acetylcholine receptors (AChRs) on cultured myotubes to aggregate into patches. Our previous studies have indicated that the active component of these extracts is similar to the molecules in the basal lamina which direct the aggregation of AChRs in the muscle fibre plasma membrane at regenerating neuromuscular junctions in vivo. Because it can be obtained in large amounts and assayed in controlled conditions in cell culture, the AChR-aggregating factor from electric organ may be especially useful for examining in detail how the postsynaptic apparatus of regenerating muscle is assembled. Here we demonstrate that the electric organ factor causes not only the formation of AChR aggregates on cultured myotubes, but also the formation of patches of acetylcholinesterase (AChE). This finding, together with the observation that basal lamina directs the formation of both AChR and AChE aggregates at regenerating neuromuscular junctions in vivo, leads us to hypothesize that a single component of the synaptic basal lamina causes the formation of both these synaptic specializations on regenerating myofibres.     

The molecular mechanism by which insulin stimulates glycogen synthesis in mammalian skeletal muscle

The ability of insulin to promote the phosphorylation of some proteins and the dephosphorylation of others is paradoxical. An insulin-stimulated protein kinase is shown to activate the type-1 protein phosphatase that controls glycogen metabolism, by phosphorylating its regulatory subunit at a specific serine. Furthermore, the phosphorylation of this residue is stimulated by insulin in vivo. Increased and decreased phosphorylation of proteins by insulin can therefore be explained through the same basic underlying mechanism.     

Regulation of a protein synthesis initiation factor by adenovirus virus-associated RNA

A small RNA accumulating late in adenovirus infection is required for efficient protein synthesis, although not specifically for the translation of viral proteins. This RNA maintains the activity of an initiation factor catalysing the earliest step of polypeptide chain initiation.     

A point mutation in the neu oncogene mimics ligand induction of receptor aggregation

The rat neu gene, which encodes a protein closely related to the epidermal growth factor receptor, is a proto-oncogene that can be converted into an oncogene by a point mutation. Both genes encode proteins with a relative molecular mass of 185,000 but the question of why the neu gene product, p185neu, is oncogenic, whereas the product of c-neu, p185c-neu, is not, remains unanswered. The proteins have several features common to the family of tyrosine kinase growth-factor receptors, including cysteine-rich external domains, a hydrophobic transmembrane region and a cytoplasmic tyrosine kinase domain. The oncogenic p185neu differs from p185c-neu by an amino-acid substitution in the transmembrane region of the glycoprotein: this replacement of valine by glutamic acid at position 664 induces increased intrinsic tyrosine kinase activity which is associated with transformation. Many glycoproteins with charged amino acids in the transmembrane region exist as multimeric complexes at the plasma membrane. We have therefore investigated the association state of both products of the neu gene and show that the oncoprotein p185neu is organized at the plasma membrane primarily in an aggregated form, but that p185c-neu is not. Induction of an aggregated state may mimic aspects of ligand-induced receptor aggregation resulting in enzymatic activation that leads to cellular transformation.