| ne of the most striking features of a nerve terminal is the abundance of small translucent synaptic vesicles (small synaptic vesicles: SSVs) that cluster at the presynaptic site. These vesicles store and secrete "classical" non-peptide neurotransmitters such as glutamate, GABA and acetylcholine, which are responsible for the rapid signal transduction typically associated with neurons.;Many neurons secrete neuropeptides in addition to the classical neurotransmitters. Neuropeptides are stored in large-dense core vesicles (LDCVs) which are less abundant than SSVs in most nerve terminals. LDCVs are similar to peptide-containing secretory granules of endocrine cells and can be regarded as the neuronal equivalent: the biochemical nature of their content is similar and the organelles have a similar pathway of biogenesis.;Several of the SSV membrane proteins have been identified and characterized. It is now known that these proteins are also expressed in endocrine cells, where they are localized to a population of microvesicles distinct from secretory granules. Due to their biochemical similarity with SSVs, these organelles are referred to as synaptic-like microvesicles (SLMVs). The function of SLMVs is unknown. However, given their close biochemical relationship to SSVs, it is possible they also store and secrete neurotransmitter molecules. In order to test this hypothesis we have chosen the ;GABA is the major inhibitory neurotransmitter in the brain. It is also thought to act as a paracrine signal molecule in pancreatic islets. The islets are composed of distinct subpopulations of endocrine cells of which only the insulin-secreting ;In this thesis, evidence is presented here to support this idea. We have demonstrated the existence of SLMVs in insulin-secreting... |
