Commentary: Neurotransmitter Secretion and Cell Signaling

Abstract

Many proteins involved in neurotransmitter release have been identified, but how these molecules interact and function together to mediate neurotransmission is not completely known. Chromaffin cells have been one of the favorite models for the study of the molecular mechanism of exocytosis and regulation of the differential release of catecholamine and peptides co-stored in the chromaffin granules. Several talks were presented at this meeting, describing the function of different molecules in regulating neurotransmitter secretion and synaptic transmission. Corey Smith (USA) reported that by using various frequencies to mimic basal and acute sympathetic activity to stimulate chromaffin cells, he was able to demonstrate that differential release of neurotransmitters is regulated by the opening of the fusion pore mediated by an interaction between syndapin and dynamin. Xuelin Lou (USA) presented new data on the role of dynamin isoforms in synaptic transmission by showing that presynaptic dynamin 3 function synergizes with dynamin 1. Significantly, neurons lacking both dynamins develop, differentiate, and establish synapses in vitro. But most strikingly, nerve terminals can recycle synaptic vesicles in the absence of both dynamins, implying that dynamin 2 alone and/or dynamin independent mechanisms are sufficient to support basic synaptic function. These results collectively demonstrate that neither dynamin 1 nor 3 are essential for regenerating synaptic vesicles, but rather contribute to the efficiency of this process. Chen Zhang (China) discussed the role of presenilin, a molecule implicated in the pathogenesis of Alzheimer’s disease, in neurotransmitter secretion. He used genetic approaches to conditionally inactivate the protein in presynaptic and postsynaptic neurons in the hippocampus. His results showed that only presynaptic, but not postsynaptic inactivation of presenilin impaired synaptic activity and this impairment was induced by modulation of Ca release from the endoplasmic reticulumCa stores.Kathrin Engisch (USA) used the isolated mouse chromaffin cells to study the effects of levetiracetam, an anticonvulsant that binds to the synaptic vesicle protein SV2A on neurotransmitter release. She showed that levetiracetam decreases the high activity-induced Ca currents and secretion but had no effect on the resting cells. The results may shed some light on the pharmacology of the drug on neurotransmission. The effects of some molecules on catecholamine secretion were also presented. Damien Keating (Australia) discussed interesting results on the molecular mechanism of exocytosis regulated by HAP1, Huntingtin-associated protein 1. Kevin Curie (USA) reported the paracrine effects of PGE2 on the secretion, possibly mediated by EP3 receptor. Daniel O’Connor (USA) reported a systematic study of the polymorphism found in the enzymes involved in catecholamine biosynthesis. G-protein coupled receptors (GPCR) and glutamate receptors play major roles in cell signaling. Duk-Su Koh (USA) presented studies on glutaminergic signaling in pancreatic islets. Extending his presentation at the meeting, he has provided a comprehensive review (below) on how islet hormones such as insulin and glucagon act as paracrine or autocrine modulators of neighboring cells in the pancreatic islets to regulate glucose levels. In addition, he has described a role of excitatory glutamate and inhibitory γ-amino butyric L.-S. Kao Department of Life Sciences and Institute of Genome Sciences, Brain Research Center, National Yang-Ming University, Taipei, Taiwan e-mail: lskao@ym.edu.tw