MECHANISMS OF TRANSMITTER SECRETION AT SYMPATHETIC NERVE VARICOSITIES
Funder
National Health and Medical Research Council
Funding Amount
$438,707.00
Summary
The mechanism by which quantal packets of transmitter are secreted from release sites called varicosities on sympathetic nerve terminals can now be taken to the molecular level, given the new techniques which we have introduced to solve this problem. There are two main facets to the problem. The first of these involves the question of how proteins involved in controlling the regulated secretion or exocytosis of the quantal packets of transmitter carry out this function. These proteins (syntaxin, ....The mechanism by which quantal packets of transmitter are secreted from release sites called varicosities on sympathetic nerve terminals can now be taken to the molecular level, given the new techniques which we have introduced to solve this problem. There are two main facets to the problem. The first of these involves the question of how proteins involved in controlling the regulated secretion or exocytosis of the quantal packets of transmitter carry out this function. These proteins (syntaxin, synaptobrevin, SNAP25 and synaptotagmin) together with a calcium channel are complexed with a docked synaptic vesicle containing a quantum of transmitter in a module of secretion appropriately called a secretosome. The leading questions here are to determine if only a single secretosome participates in transmitter release on the arrival of a nerve impulse, whether the number of these secretosomes in a varicosity determines its probability for secretion of a quantum, and fundamentally, how do the proteins within the secretosome cooperate to trigger exocytosis when there is sufficient calcium influx through the secretosome-associated calcium channel following the impulse. The other problem concerns the mechanism of removal of calcium from the varicosity once it has entered through the channels, This calcium can have considerable affects on the extent to which secretosomes participate in secretion with subsequent impulses. Furthermore, this influx of calcium can be modulated for subsequent impulses by transmitter released by the first impulse. The present research will solve these problems, providing a molecular description of secretion from single sympathetic varicosities.Read moreRead less
A -induced Cell Death Signalling By The P75 Neurotrophin Receptor.
Funder
National Health and Medical Research Council
Funding Amount
$546,382.00
Summary
The amyloid peptide A is central to the cause of Alzheimer's disease. We have recently found that A can activate the cell death receptor p75NTR which is found in the nerve cells that die in Alzheimer's disease. This project will study whether this death pathway underpins the neuronal death associated with Alzheimer's disease. It will also determine the mechanism by which A activates p75NTR death signalling, and identify biochemical ways to prevent this from occurring.