Obiettivo
To analyse the mechanisms which govern neurotransmitter release in neurons, or in neuronal cell lines.
To contribute to our understanding of the transmitter organelle/vesicle life cycle within the neuron.
To study the processing of neuropeptides in the life-cycle of peptide containing organelles in different neurons.
To investigate the intraneuronal transport and regulation of transmitter vesicle associated molecules essential for transmitter release from "adrenergic" and "cholinergic" nerve terminals. We have focussed on the autonomic nervous component, using catecholamines or acetylcholine as "classical transmitters" because they are easily accessible to physiological, pharmacological and morphological studies, and these systems are well known to all participants in the network.
To clarify the physiological relationship between small synaptic vesicles (SSV), small dense cored vesicles (SDV) and large dense cored vesicles (LDV).
n this project we concentrate on the intraneuronal transport and regulation of transmitter vesicle associated molecules essential for transmitter release from "adrenergic" and "cholinergic" nerve terminals. It is now well established that neurons can secrete not only classical transmitters but also e.g. peptides (see above). According to the current concept the classical transmitters are stored in small synaptic vesicles (SSV) which are loaded in the nerve terminal and are continuously regenerated by local recycling. In contrast to the classical transmitters, the neuropeptides are stored in and released from the large dense cored vesicles (LDV). In neurons which release NA or ACh these LDV are packed with precursor protein/peptides at the level of the Golgi after which the fully assembled vesicles are transported to the release sites. Exocytosis of LDV and SSV is considered to be differentially regulated and take place at distinct release sites. In noradrenergic neurons SSV have an electron dense matrix due to the presence of NA (after certain fixation techniques), and are called small dense cored vesicles (SDV).
Characterization of the protein composition of the SSV membrane and identification of a number of G-proteins involved in regulating vesicle traffic, have largely contributed to an understanding of the life cycle of the SSV and have lead to a "unitarian neuron" as a working model.
However, this might well be an oversimplification and it is likely that different neuronal systems with different neurotransmitters and different physiology in the organism have developed modifications of the common "theme" of release. For example, in peripheral postganglionic neurons of the autonomic nervous system (ANS) the classical transmitter (NA) is not only present in SDV but also in the LDV. Another example of adaptation is the vesicle protein VAMP, a molecule which probably is necessary for docking vesicles to the presynaptic membrane before release. This protein exists in two isoforms, VAMP I and VAMP II which are ncoded by different genes. VAMP I is present in postganglionic adrenergic neurons but VAMP II is not. An even more drastic difference, however, is the recent evidence that in noradrenergic neurons, the classical transmitter appears to be released not from SDV primarily, but from LDV, which is in contrast to previous reports. These data are in contradiction with the "unitarian model". Thus, more work is needed to unravel the complete membrane cycles of SDV, SSV, and LDV in peripheral postganglionic noradrenergic and cholinergic neur.
The adrenal medulla has been very useful for the study of adrenergic neurons, since these cells are ontogenetically adrenergic neurons which have been prevented from growing neurites due to the continous inhibitory influence from corticosteroids secreted from the adrenal cortex and flooding the medulla via the venous dainage from cortex to medulla. The large source of catecholamine storage organelles from this organ has greatly advanced our knowledge about mechanisms of storage and release from adrenergic neurons. It was recen discovered that the adrenal medulla also contain SSV-like vesicles, but the function of these are so far unclear. In this proposal we like to take advantage of the adrenal medulla, in addition of cell culture systems of cell lines derived from neuronal sources.
The participants in this study will use a combination of biochemical, morphological and immunochemical techniques to study components of the SSV, SDV and LDV in adrenergic and cholinergic neurons, as well as in adrenal medulla and in culture systems of neuronally derd cell lines. The participating groups have been selected on the basis of complementary techniques, material and expertize. Our view is that the molecular machinery that controls the life cycle of transmitter organelles is of utmost importance in controlling the function of the axon terminal as such and of transmitter release. Faults in the machinery that govern synaptic organelle life cycle within the nerve cell will have dramatic consequences for the synaptic transmission process. This possibility has so far not been considered en models for defects in neural signalling were developed.
Campo scientifico (EuroSciVoc)
CORDIS classifica i progetti con EuroSciVoc, una tassonomia multilingue dei campi scientifici, attraverso un processo semi-automatico basato su tecniche NLP. Cfr.: Il Vocabolario Scientifico Europeo.
CORDIS classifica i progetti con EuroSciVoc, una tassonomia multilingue dei campi scientifici, attraverso un processo semi-automatico basato su tecniche NLP. Cfr.: Il Vocabolario Scientifico Europeo.
- scienze naturali scienze biologiche neurobiologia
- ingegneria e tecnologia ingegneria ambientale gestione dei rifiuti processi di trattamento dei rifiuti riciclaggio
- scienze naturali scienze biologiche biochimica biomolecole proteine
- scienze mediche e della salute medicina di base fisiologia
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Gli inviti a presentare proposte sono suddivisi per argomenti. Un argomento definisce un’area o un tema specifico per il quale i candidati possono presentare proposte. La descrizione di un argomento comprende il suo ambito specifico e l’impatto previsto del progetto finanziato.
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Meccanismo di finanziamento (o «Tipo di azione») all’interno di un programma con caratteristiche comuni. Specifica: l’ambito di ciò che viene finanziato; il tasso di rimborso; i criteri di valutazione specifici per qualificarsi per il finanziamento; l’uso di forme semplificate di costi come gli importi forfettari.
Coordinatore
40530 GOTEBORG
Svezia
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