Microtubule Capture By E-cadherin: A Novel Mechanism For Dynamic Cell-cell Adhesion.
Funder
National Health and Medical Research Council
Funding Amount
$439,500.00
Summary
This project studies the molecular mechanisms responsible for holding cells together in normal tissues. Such cell-to-cell adhesion is mediated by the cadherin family of molecules, which reside at the surfaces of cells. Cadherins allow cells to recognize one another and, upon recognition, adhere to one another. By this means populations of individual cells can be linked together into cohesive populations (i.e. the tissues or organs of the body). The importance of cadherin adhesion is exemplified ....This project studies the molecular mechanisms responsible for holding cells together in normal tissues. Such cell-to-cell adhesion is mediated by the cadherin family of molecules, which reside at the surfaces of cells. Cadherins allow cells to recognize one another and, upon recognition, adhere to one another. By this means populations of individual cells can be linked together into cohesive populations (i.e. the tissues or organs of the body). The importance of cadherin adhesion is exemplified by the well-documented observation that disruption of cadherin adhesion contributes to many important diseases, including inflammation of epithelia and cancers. Thus understanding the mechanisms by which cadherins hold cells together is necessary for us to understand the molecular basis of commondisease. It has long been known that cadherins work in cooperation with elements within the cell, called the cytoskeleton. My lab has recently made the novel discovery that microtubules, specific components of the cytoskeleton, can regulate the functionof cadherin adhesion molecules. Inparticular, microtubules appear to affect how cadherins can participate in dynamic cell processes necessary for cells to be properly organized in tissues. In this project we will probe the molecular mechanisms responsible for this effect of microtubules. The information obtained will provide important new insights into how dynamic cadherin adhesion is controlled, to help our understanding of the cellular mechanisms that couple cells into tissues, and how they may be disrupted in diesase.Read moreRead less
Cortactin: Integrating Cadherin Signalling For Junctional Integrity
Funder
National Health and Medical Research Council
Funding Amount
$593,888.00
Summary
Adhesion between cells holds the human body together and affects many aspects of our health, including normal tissue and organ function. Importantly, loss of normal cell-cell adhesion contributes to many diseases, including cancer and inflammation. One key adhesion molecule, E-cadherin, is necessary for many epithelial tissues and its function is perturbed in disease. This research project addresses how E-cadherin signals into cells to control cell-to-cell interactions.
Preserving Junctions: Regulating Cadherins By Rho And Myosin 2.
Funder
National Health and Medical Research Council
Funding Amount
$425,500.00
Summary
This project studies the molecular mechanisms responsible for holding cells together in normal tissues. Such cell-to-cell adhesion is mediated by the cadherin family of molecules, which reside at the surfaces of cells. Cadherins allow cells to recognize one another and, upon recognition, adhere to one another. By this means populations of individual cells can be linked together into cohesive populations (i.e. the tissues or organs of the body). The importance of cadherin adhesion is exemplified ....This project studies the molecular mechanisms responsible for holding cells together in normal tissues. Such cell-to-cell adhesion is mediated by the cadherin family of molecules, which reside at the surfaces of cells. Cadherins allow cells to recognize one another and, upon recognition, adhere to one another. By this means populations of individual cells can be linked together into cohesive populations (i.e. the tissues or organs of the body). The importance of cadherin adhesion is exemplified by the well-documented observation that disruption of cadherin adhesion contributes to many important diseases, including inflammation of epithelia and cancers. Thus understanding the mechanisms by which cadherins hold cells together is necessary for us to understand the molecular basis of commondisease. Characteristically, cadherins accumulate in structures called adherens junctions, and preserving those junctions is important both for tissues to organize and also to prevent tumor progression. Despite this, we know very little about how junctions are preserved in epithelia. The research to be conducted in this grant will examine exactly this problem. It builds upon recent findings from my lab which indicate that the motor molecule, myosin 2 plays an essential role in preserving junctions. Furthermore, we will test the role for signaling pathways within cells to control the activity of myosin 2 at junctions. This research will provide important novel insights into the cellular mechanisms that couple cells into tissues, and how they may be disrupted in diesase.Read moreRead less
Molecular Characterization Of E-cadherin-activated Rac Signaling
Funder
National Health and Medical Research Council
Funding Amount
$220,500.00
Summary
Interactions between cells and their neighbouring cells control many important processes in the body. The adhesion molecule, E-cadherin, is a major protein that controls interactions between cells in epithelial tissues (e.g. breast, lung, gut). E-cadherin is essential for these tissues to form normally, and loss of E-cadherin function contributes to the progression of many human cancers (especially common cancers such as breast and lung). Understanding how E-cadherin controls normal epithelial c ....Interactions between cells and their neighbouring cells control many important processes in the body. The adhesion molecule, E-cadherin, is a major protein that controls interactions between cells in epithelial tissues (e.g. breast, lung, gut). E-cadherin is essential for these tissues to form normally, and loss of E-cadherin function contributes to the progression of many human cancers (especially common cancers such as breast and lung). Understanding how E-cadherin controls normal epithelial cell function will therefore provide key insights into the bases for tumor progression. In this study we will examine how E-cadherin signals to the interior of cells. We have recently discovered a new signaling pathway that is turned on when E-cadherin is activated. Understanding the fundamental elements of this signaling pathway will provide invaluable insights into how cells recognize one another during health and disease.Read moreRead less
Cortactin: Molecular Regulation Of Cadherin Activity And Epithelial Morphogenesis.
Funder
National Health and Medical Research Council
Funding Amount
$239,250.00
Summary
Interactions between cells and their neighbouring cells control many important processes in the body. The adhesion molecule E-cadherin is a major protein that controls how cells interact with one another in many epithelial tissues (e.g. breast, lung, gut). These tissues are the source of many common diseases, particular cancer and inflammation. E-cadherin is essential for these tissues to form normally, and loss of E-cadherin function contributes to disease in these tissues (especially common ca ....Interactions between cells and their neighbouring cells control many important processes in the body. The adhesion molecule E-cadherin is a major protein that controls how cells interact with one another in many epithelial tissues (e.g. breast, lung, gut). These tissues are the source of many common diseases, particular cancer and inflammation. E-cadherin is essential for these tissues to form normally, and loss of E-cadherin function contributes to disease in these tissues (especially common cancers, such as breast and lung). Understanding how E-cadherin controls normal cell function in these tissues will therefore provide key insights into how disease arises. In this study we will investigate how a protein which binds to E-cadherin, cortactin, contributes to the biological effect of E-cadherin in supporting tissue architecture. Understanding the fundamental elements of how cortactin works with E-cadherin will provide invaluable information into how cells recognize one another in health, and fail to adequately recognize each other in common diseases.Read moreRead less
Functional Characterization Of A Signaling Complex Between Receptor Protein Tyrosine Phosphatase-k And E-cadherin.
Funder
National Health and Medical Research Council
Funding Amount
$227,036.00
Summary
Contact between cells in the body controls many aspects of cellular function, including cell adhesion, cell movenments, and the architecture of organs. These contacts involve many different kinds of molecules, such as adhesion molecules, proteins that link the cell surface to the cytoskeleton, and many signaling molecules that participate in cellular recognition. It has become increasingly clear that these different molecules interact with one another and that these interactions are functionally ....Contact between cells in the body controls many aspects of cellular function, including cell adhesion, cell movenments, and the architecture of organs. These contacts involve many different kinds of molecules, such as adhesion molecules, proteins that link the cell surface to the cytoskeleton, and many signaling molecules that participate in cellular recognition. It has become increasingly clear that these different molecules interact with one another and that these interactions are functionally important. In this proposal we will study the association between a signaling molecule, the receptor tyrosine phosphatase RPTPk, and a cell-cell adhesion molecule, E-cadherin. RPTPk removes phosphate molecules from tyrosines, an important event that controls many signaling processes; E-cadherin is a major adhesion molecule responsible for cell-cell contact and patterning, and whose dysfunction is involved in tumor invasion. My collaborators and I have recently demonstrated that RPTPk and E-cadherin bind to one another, but the function of this association is unclear. I will test the general hypothesis that these molecules form a signaling complex, that can regulate both the activity of RPTPk and the adhesive function of E-cadherin to ultimately control the way in which cells associate with one another. This work will make an important contribution to our understanding of how cells signal to one another, and provide insights into how cell-cell adhesion and recognition may be perturbed in disease conditions, such as tumor progression.Read moreRead less