Neuronal communication relies on the process of exocytosis by which neurons release a neurotransmitter. Exocytosis is critical for the simplest muscle movement to complex tasks such as learning and memory, and is altered in several neurodegenerative pathologies. We will investigate how the protein Munc18 controls exocytosis. This research will be important for understanding how neurons communicate in health and disease and will be relevant to other processes such as insulin release in diabetes.
Modulating Neuronal Secretion By The PI3-kinase Pathway
Funder
National Health and Medical Research Council
Funding Amount
$516,855.00
Summary
Neuronal communication relies on the process of exocytosis by which neurons release neurotransmitter. Exocytosis is critical for the simplest reflex movement to complex tasks such as learning and memory, and is altered in several neurodegenerative pathologies. We will investigate how certain lipids control exocytosis. This research is important for understanding how neurons communicate in health and disease and is relevant to other processes such as insulin release in diabetes.
Differential Regulation Of Two Modes Of Exocytosis By Protein Phosphatases
Funder
National Health and Medical Research Council
Funding Amount
$399,750.00
Summary
The release of signals from nerve endings (exocytosis) is of fundamental importance to nervous system function. The recent recognition that nerve cells can release transmitter by at least two distinct modes of exocytosis has led to the need for a deeper understanding of the mechanisms that regulate exocytosis. Our identification of the key role played by two enzymes, PP2A and PP2B, represents a major insight into the molecular mechansisms regulating this process. The experiments will lead to the ....The release of signals from nerve endings (exocytosis) is of fundamental importance to nervous system function. The recent recognition that nerve cells can release transmitter by at least two distinct modes of exocytosis has led to the need for a deeper understanding of the mechanisms that regulate exocytosis. Our identification of the key role played by two enzymes, PP2A and PP2B, represents a major insight into the molecular mechansisms regulating this process. The experiments will lead to the identification of how PP2A and PP2B are regulated at the molecular level and the targets that are important in the control of exocytosis. The project will also develop new tools to specifically manipulate the two modes of exocytosis in order to understand their contribution to normal and pathological neurotransmission. Strong stimulation of exocytosis is associated with learning and memory in normal brain and neuronal damage under certain pathological conditions. Since switching from 1 mode of exocytosis to another is also induced by strong stimulation, an understanding of the molecular mechanisms that control the different modes of exocytosis may eventually lead to clinical applications.Read moreRead less
TNF Traffic And Secretion In Astrocytes And Microglial Cells: Unveilling New Targets For Ischemic Stroke
Funder
National Health and Medical Research Council
Funding Amount
$585,070.00
Summary
Neurodegenerative disorders share a similar pathway to disastrous neurotoxicity, which occurs through the release of cytokines such as tumour necrosis factor-a (TNF) from glial cells. TNF controls inflammation but its excessive secretion in the brain is highly detrimental. The mechanism of TNF secretion is unknown but strategies aimed at reducing it have therapeutic potential. This grant proposes to study TNF discharge to find new ways to reduce secretion and confer protection in a stroke model.