PKA-catalyzed phosphorylation of tomosyn and its implication in Ca2+-dependent exocytosis of neurotransmitter

Neurotransmitter is released from nerve terminals by Ca2+-dependent exocytosis through many steps. SNARE proteins are key components at the priming and fusion steps, and the priming step is modulated by cAMP-dependent protein kinase (PKA), which causes synaptic plasticity. We show that the SNARE regulatory protein tomosyn is directly phosphorylated by PKA, which reduces its interaction with syntaxin-1 (a component of SNAREs) and enhances the formation of the SNARE complex. Electrophysiological studies using cultured superior cervical ganglion (SCG) neurons revealed that this enhanced formation of the SNARE complex by the PKA-catalyzed phosphorylation of tomosyn increased the fusion-competent readily releasable pool of synaptic vesicles and, thereby, enhanced neurotransmitter release. This mechanism was indeed involved in the facilitation of neurotransmitter release that was induced by a potent biological mediator, the pituitary adenylate cyclase-activating polypeptide, in SCG neurons. We describe the roles and modes of action of PKA and tomosyn in Ca2+-dependent neurotransmitter release

Continuous monitoring of groundwater radon for evaluating chemical and structural properties and fluid flow variations of shallow aquifer systems

We have carried out continuous monitoring of radon concentration in groundwater at eight wells in Nishinomiya City, Hyogo Prefecture, Japan. The shallowest major aquifer, which we call the first aquifer, extends widely at a depth about 3-5 meters in the region. We pay our major attention to the first aquifer, because it provides us with abundant high quality water, which has long been utilized for brewing Sake. We made the radon monitoring at 5 wells tapping the first aquifer. The first aquifer can be characterized by very high radon concentration and its large temporal variation. Time-averaged values of radon concentration at 4 shallow wells were about 70-80 Bq/l, which is almost the highest value ever reported for natural water throughout the Japanese Islands. These high radon concentrations can be attributed to uranium-rich sediments in the aquifer, which had been brought from the Rokko Mountains region on the north. Large temporal variations of radon concentration observed at the shallow wells probably reflect the heterogeneous distribution of the grain size of sediments, which makes the groundwater flow unstable. We examined radon concentrations in deeper aquifers at three wells with depths of 8-17 m for comparison. Absolute values of radon concentrations and their temporal variations at the deeper wells are smaller than those in the first aquifer, which suggests the small contributions of uranium-rich sands to the sediments compared with the first aquifer. The radon concentration at a well with a depth of 16 m showed periodical variations responding to the ocean tide, which demonstrates that very small signals of crustal deformations can be detected by the continuous monitoring of groundwater radon

Regulation of SNAREs by tomosyn and ROCK: implication in extension and retraction of neurites

Extension of neurites requires the SNARE-dependent fusion of plasmalemmal precursor vesicles with the plasma membrane of growth cones. Here, we show that tomosyn localizes at the palm of growth cones and inhibits the fusion of the vesicles there, thus promoting transport of the vesicles to the plasma membrane of the leading edges of growth cones. Tomosyn localizes because ROCK activated by Rho small G protein phosphorylates syntaxin-1, which increases the affinity of syntaxin-1 for tomosyn and forms a stable complex with tomosyn, resulting in inhibition of the formation of the SNARE complex. In retraction of neurites, tomosyn localizes all over the edges of the neurites and inhibits fusion of the vesicles with the plasma membrane. Thus, tomosyn demarcates the plasma membrane by binding to syntaxin-1 phosphorylated by ROCK, and thereby regulates extension and retraction of neurites

Schwannoma resembling metastatic lymph node

In this report, we describe a rare case of vagus nerve schwannoma associated with esophageal cancer. A 70-year-old man visited our hospital complaining of worsening dysphagia. His upper gastrointenstinal endoscopy revealed a mass in the esophagus. A contrast-enhanced chest computed tomography also detected a 15 mm nodule attached to the tracheal membrane. This nodule was diagnosed as a metastatic lymph node. Although the primary tumor reduced after neoadjuvant chemotherapy, the nodule remained intact ; it showed fluorodeoxyglucose accumulation on positron emission tomography. We had a clinical diagnosis of stage III after neoadjuvant chemotherapy and underwent surgery. Intraoperatively, the nodule could not be detached from the right vagus nerve ; therefore, we excised the nodule along with the adjacent vagus nerve. The nodule was pathologically diagnosed as a vagus schwannoma. The nodule was not a regional lymph node metastasis of esophageal cancer. His postoperative course was uneventful, and he is currently undergoing outpatient follow-up without recurrence