How vesicular transport participates in neurite outgrowth is still poorly understood. Neurite outgrowth is not sensitive to tetanus neurotoxin thus does not involve synaptobrevin-mediated vesicular transport to the plasma membrane of neurons. Tetanus neurotoxin-insensitive vesicle-associated membrane protein (TI-VAMP) is a vesicle-SNARE (soluble N-ethylmaleimide-sensitive fusion protein [NSF] a...

SNAP-25 (25 kDa synaptosome-associated protein) is found in cells that release neurotransmitters and hormones, and plays a central role in the fusion of secretory vesicles with the plasma membrane. SNAP-25 has been shown to interact specifically with syntaxin 1, a 35 kDa membrane protein, to mediate the fusion process. Here, we investigated whether other known syntaxin isoforms found at the pla...

The effects and modes of action of certain lipid second messengers and protein kinase C regulators, such as sphingosine, lysophosphatidylcholine (lyso-PC), and oleic acid, on Na,K-ATPase and sodium pump were examined. Inhibition of purified rat brain synaptosome Na,K-ATPase by these lipid metabolites, unlike that by ouabain, was subject to membrane dilution (i.e. inhibition being counteracted b...

The sodium pump is the enzyme responsible for the maintenance of Na+ and K+ gradients across the cell membrane. Four isoforms of the catalytic alpha subunit have been identified, but their individual roles remain essentially unknown. To investigate the necessary functions of the alpha2 subunit in vivo, we generated and analyzed mice defective in the alpha2 subunit gene. Mice homozygous for the ...

Local protein synthesis in dendrites contributes to the synaptic modifications underlying learning and memory. The mRNA encoding the α subunit of the calcium/calmodulin dependent Kinase II (CaMKIIα) is dendritically localized and locally translated. A role for CaMKIIα local translation in hippocampus-dependent memory has been demonstrated in mice with disrupted CaMKIIα dendritic translation, th...

Taste bud cells (TBCs) express various neurotransmitter receptors assumed to facilitate or modify taste information processing within taste buds. We investigated the functional expression of muscarinic acetylcholine receptor (mAChR) subtypes, M1-M5, in mouse fungiform TBCs. ACh applied to the basolateral membrane of TBCs elevates the intracellular Ca(2+) level in a concentration-dependent manne...

We investigated oxidative stress in human postmortem frontal cortexfrom individuals characterized as mild cognitive impairment (n= 8), mild/moderate Alzheimer disease (n = 4), and late-stage Alzheimer disease (n = 9). Samples from subjects with no cognitive impairment (n = 10) that were age- and postmortem interval-matched with these cases were used as controls. The short postmortem intervalbra...

The tubulovesicles of gastric parietal cells sequester H+/K+-ATPase molecules within resting parietal cells. Stimulation of parietal cell secretion elicits delivery of intracellular H+/K+-ATPase to the apically oriented secretory canaliculus. Previous investigations have suggested that this process requires the regulated fusion of intracellular tubulovesicles with the canalicular target membran...

Previous investigations in our laboratory revealed that N-methyl-D-aspartate (NMDA) and L-glutamate stimulate [3H]noradrenaline release in rat brain cortex slices (Fink et al., 1989; G&hert and Fink, 1989). However, the exact location of the NMDA receptor involved remained unclear. Tetrodotoxin strongly reduced the stimulatory effect of NMDA but failed to completely abolish it. This finding wou...

Schizophrenia is a common psychiatric disorder with high heritability and complex genetic architecture. Genome-wide association studies (GWAS) have identified several significant loci associated with schizophrenia. However, the explained heritability is still low. Growing evidence has shown schizophrenia is attributable to multiple genes with moderate effects. In-depth mining and integration of...