Cytoskeletal Regulation Of Platelet Adhesion And Thrombus Formation
Funder
National Health and Medical Research Council
Funding Amount
$406,527.00
Summary
Platelets are small specialised blood cells that are essential for normal blood clotting and repair of damaged blood vessels following injury. When platelets stick to sites of blood vessel injury they undergo dramatic changes in their shape and internal structure that are necessary for these cells to spread over the damaged surface and facilitate the formation of a stable blood clot. We are studying these changes in the intracellular structure (cytoskeleton) of platelets and how these events mig ....Platelets are small specialised blood cells that are essential for normal blood clotting and repair of damaged blood vessels following injury. When platelets stick to sites of blood vessel injury they undergo dramatic changes in their shape and internal structure that are necessary for these cells to spread over the damaged surface and facilitate the formation of a stable blood clot. We are studying these changes in the intracellular structure (cytoskeleton) of platelets and how these events might regulate the reactivity of platelets and their ability to adhere to blood vessels. An understanding of these processes will add significantly to our knowledge of how blood clots. This information is relevant to many human diseases such as heart attack and stroke.Read moreRead less
Following a meal glucose circulates in the blood and is taken up into cells via movement of an intracellular glucose transporter from the inside of the cell to fuse with the cell membrane and subsequent transfer of the glucose into the cell. This process is triggered by insulin. One of the commonest diseases resulting from a failure of this cellular process is diabetes. A common form of diabetes which occurs in many adults in Australia results from insulin resistance, whereby the effects of insu ....Following a meal glucose circulates in the blood and is taken up into cells via movement of an intracellular glucose transporter from the inside of the cell to fuse with the cell membrane and subsequent transfer of the glucose into the cell. This process is triggered by insulin. One of the commonest diseases resulting from a failure of this cellular process is diabetes. A common form of diabetes which occurs in many adults in Australia results from insulin resistance, whereby the effects of insulin are diminished and cells become increasingly unable to uptake glucose. Recent studies have demonstrated that a novel enzyme known as SHIP-2 may play a role in regulating insulin action in cells. Deletion of SHIP-2 in mice results in these animals have increased sensitivity to insulin, low blood glucose levels, and a greatly enhanced ability to take up glucose in cells in response to low dose insulin. Our laboratory has been working on the cellular mechanisms regulating SHIP-2 function. We have recently revealed the intracellular location of SHIP-2 and also demonstrated how SHIP-2 is localized in the cell. These studies have shown that SHIP-2, via interactions with other proteins, regulates the actin cytoskeleton immediately beneath the cell membrane and this may be a mechanism for facilitating cellular glucose uptake. This research proposal aims to determine how SHIP-2 facilitates glucose uptake into cells. We will make cell lines and transgenic animals which express high levels of this enzyme and determine the functional consequences on insulin stimulated glucose uptake. Collectively these studies in the long term may facilitate better treatment strategies for diabetic patients.Read moreRead less