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Z E Tóth

Publications and source records attributed to Z E Tóth.

6 recordsLinked to original sources

Interaction of neuronal calcium sensor-1 (NCS-1) with phosphatidylinositol 4-kinase beta stimulates lipid kinase activity and affects membrane trafficking in COS-7 cells.

Phosphatidylinositol 4-kinases (PI4K) catalyze the first step in the synthesis of phosphatidylinositol 4,5-bisphosphate, an important lipid regulator of several cellular functions. Here we show that the Ca(2+)-binding protein, neuronal calcium sensor-1 (NCS-1), can physically associate with the type III PI4Kbeta with functional consequences affecting the kinase. Recombinant PI4Kbeta, but not its glutathione S-transferase-fused form, showed enhanced PI kinase activity when incubated with recombinant NCS-1, but only if the latter was myristoylated. Similarly, in vitro translated NCS-1, but not its myristoylation-defective mutant, was found associated with recombinant- or in vitro translated PI4Kbeta in PI4Kbeta-immunoprecipitates. When expressed in COS-7 cells, PI4Kbeta and NCS-1 formed a complex that could be immunoprecipitated with antibodies against either proteins, and PI 4-kinase activity was present in anti-NCS-1 immunoprecipitates. Expressed NCS-1-YFP showed co-localization with endogenous PI4Kbeta primarily in the Golgi, but it was also present in the walls of numerous large perinuclear vesicles. Co-expression of a catalytically inactive PI4Kbeta inhibited the development of this vesicular phenotype. Transfection of PI4Kbeta and NCS-1 had no effect on basal PIP synthesis in permeabilized COS-7 cells, but it increased the wortmannin-sensitive [(32)P]phosphate incorporation into phosphatidylinositol 4-phosphate during Ca(2+)-induced phospholipase C activation. These results together indicate that NCS-1 is able to interact with PI4Kbeta also in mammalian cells and may play a role in the regulation of this enzyme in specific cellular compartments affecting vesicular trafficking.

1-Phosphatidylinositol 4-Kinase↗

Distribution of mRNA for vanilloid receptor subtype 1 (VR1), and VR1-like immunoreactivity, in the central nervous system of the rat and human.

The cloned vanilloid receptor VR1 has attracted recent attention as a molecular integrator of painful stimuli on primary sensory neurons. The existence of vanilloid-sensitive neurons in the brain is, however, controversial. In this study, we have used an antibody and a complementary RNA probe to explore the distribution of neurons that express VR1 in rat and in certain areas of human brain. In the rat, we observed VR1-expressing neurons throughout the whole neuroaxis, including all cortical areas (in layers 3 and 5), several members of the limbic system (e.g., hippocampus, central amygdala, and both medial and lateral habenula), striatum, hypothalamus, centromedian and paraventricular thalamic nuclei, substantia nigra, reticular formation, locus coeruleus, cerebellum, and inferior olive. VR1-immunopositive cells also were found in the third and fifth layers of human parietal cortex. Reverse transcription-PCR performed with rat VR1-specific primers verified the expression of VR1 mRNA in cortex, hippocampus, and hypothalamus. In the central nervous system, neonatal capsaicin treatment depleted VR1 mRNA from the spinal nucleus of the trigeminal nerve, but not from other areas such as the inferior olive. The finding that VR1 is expressed not only in primary sensory neurons but also in several brain nuclei is of great importance in that it places VRs in a much broader perspective than pain perception. VRs in the brain (and putative endogenous vanilloids) may be involved in the control of emotions, learning, and satiety, just to name a few exciting possibilities.

Animals↗

Decussations of the descending paraventricular pathways to the brainstem and spinal cord autonomic centers.

Decussations of descending fibers of the hypothalamic paraventricular nucleus (PVN) were investigated by using Phaseolus vulgaris-leucoagglutinin (PHA-L) in intact and brainstem-operated rats. Fibers descend ipsilaterally along the brainstem and spinal cord and decussate at four levels: 1) Supramamillary decussations (SM). PVN fibers reach this area through the lateral hypothalamus and along the third ventricle in the dorsal hypothalamus. In the posterior hypothalamus some fibers crossover in the SM and terminate in the supramamillary region bilaterally. 2) Pontine tegmentum. PVN fibers run in the lateral part of the tegmentum arching to the basis of the pons. Some fibers crossover under the fourth ventricle. The locus ceruleus and the Barrington's nucleus receive bilateral innervation with ipsilateral dominance. 3) Commissural part of the nucleus of the solitary tract (NTS). The major crossover of PVN fibers is found here. The decussated fibers form a dense network here, and loop rostralward to innervate the entire NTS. A midsagittal knife-cut through the NTS eliminated paraventricular-fibers on the contralateral side. Synaptic contacts between PHA-L-labeled boutons and tyrozine hydroxilase-positive neurons were verified in the NTS. The caudal ventrolateral medulla also receives bilateral innervation. 4) Lamina X of the thoracic spinal cord. Paraventricular fibers enter the lateral funiculus ipsilaterally and innervate the intermediolateral cell column (IML). Some fibers cross the midline ventral and dorsal to the central canal running to the contralateral IML, at the level of the decussation. Our results demonstrated that paraventricular projections form a continuous descending pathway on their side of origin, and provide crossover fibers which may terminate segmentally without forming long tracts after crossover.

Animals↗

Distributions of periventricular projections of the paraventricular nucleus to the median eminence and arcuate nucleus.

Neuronal projections from the periventricular subnucleus of the hypothalamic paraventricular nucleus to the median eminence and the arcuate nucleus were investigated in the rat by the anterograde tract-tracer, Phaseolus vulgaris leucoagglutinin. The vast majority of labeled fibers coursed ventrally along the third ventricle and distributed in the external layer of the median eminence bilaterally, with ipsilateral predominance moving caudalwards. Periventricular fibers also terminated in the arcuate nucleus, but this innervation was exclusively ipsilateral.

Animals↗