Role of G-septin and its phosphorylation by PKG in nerve terminals [ 2001 - 2003 ]

Research Grant

Researchers: Prof Phillip Robinson (Principal investigator)

Brief description Nerve cells have unique properties like their ability to put out axons that reach long distances from the cell body (differentiation), their ability to make contacts with other cells and initiate communication by the release of neurotransmitters from nerve endings (exocytosis). These events are partly controlled by a signalling molecule, cGMP, which mainly stimulates the enzyme PKG. However, it has been largely unknown how PKG takes the signalling further. In previous studies supported by the NHMRC we identified 3 proteins that are phosphorylated and activated by PKG: SF1 controls the expression of genes in all cells; N-STOP stabilises the microtubule cytoskeleton to facilitate neuronal differentiation; and G-septin, which is the focus of this proposal. We cloned G-septin as the 8th member of a family of genes that are essential for cell division. Some septins assemble as filaments that allow the two new daughter cells to finally separate. When the filament formation is perturbed certain septins end up in microscopic clumps that are found in the post-mortem brains of people affected by Alzheimer's disease, suggesting they might contribute to the disease. However, G-septin is a brain-specific septin, which we found in neurons and in nerve terminals, locations not normally associated with cell division. The only other known brain-specific septin, CDCrel-1, was recently found to regulate the protein machinery of exocytosis, but is an unlikely target for cGMP. We will examine the hypothesis that G-septin is also a regulator of exocytosis. We will determine whether G-septin represents a convergence point for cGMP signalling to control exocytosis. A better understanding of G-septin and exocytosis is crucial to understanding brain disorders and ultimately developing better therapies.

Funding Amount $AUD 363,055.08

Funding Scheme NHMRC Project Grants

Notes Standard Project Grant