Sorting Nexins And Their Role In Endosomal Trafficking
Funder
National Health and Medical Research Council
Funding Amount
$331,000.00
Summary
Cells are able to internalise molecules via membrane-bound vesicles, a process known as endocytosis. Endocytosis is fundamental for many cellular processes, including receptor signalling, uptake of many essential nutrients and the ability to mount an effective lymphocyte response to foreign antigens. Once internalised, cargo is then sorted to different intracellular destinations of the endosomal transport system. The ultimate destination depends on the particular cargo molecule. The importance o ....Cells are able to internalise molecules via membrane-bound vesicles, a process known as endocytosis. Endocytosis is fundamental for many cellular processes, including receptor signalling, uptake of many essential nutrients and the ability to mount an effective lymphocyte response to foreign antigens. Once internalised, cargo is then sorted to different intracellular destinations of the endosomal transport system. The ultimate destination depends on the particular cargo molecule. The importance of the endosomal transport system is also highlighted by the discovery that many human diseases, including various cancers, lysosomal storage diseases and hypercholesterolemia, are linked to defects in trafficking along the endocytic pathway. Furthermore, a number of viral pathogens, such as HIV, and toxins, such as shiga toxin, exploit the endosomal system to gain entry into a cell. Understanding the molecular details of the sorting events within the endosomal system is necessary to be able to consider therapeutic manipulation of the trafficking of specific cargo molecules. The study seeks to understand the molecular details of the endosomal sorting machinery, knowledge that will underpin future efforts to develop drugs to manipulate movement of proteins within the endosomal system. In the long term, this could allow for the manipulation of a variety of cellular functions including the inhibition of proliferative signals in tumour cells.Read moreRead less
The Regulation And Function Of Cadherin-mediated Adhesion Within The Zebrafish Myotome.
Funder
National Health and Medical Research Council
Funding Amount
$436,773.00
Summary
Co-ordinating how cells interact with their neighbours and where different cells are positioned within an organ is the role of proteins termed cell adhesion molecules. They delineate and sort cells into different groups depending on which cell adhesion molecules are expressed on their surface. Cell adhesion molecules are also important during the onset of disease, in particular cancer, where the levels and type of cell adhesion molecules expressed on the surface of a cancer cell can determine ho ....Co-ordinating how cells interact with their neighbours and where different cells are positioned within an organ is the role of proteins termed cell adhesion molecules. They delineate and sort cells into different groups depending on which cell adhesion molecules are expressed on their surface. Cell adhesion molecules are also important during the onset of disease, in particular cancer, where the levels and type of cell adhesion molecules expressed on the surface of a cancer cell can determine how invasive or aggressive the cancer cell will become. However, despite the fundamental importance that cell adhesion plays in sorting out cells in every tissue, the exact basis of cell migratory behaviours that occur within the intact organism remain poorly defined. We have examined the ability of specific members of a particular class of cell adhesion molecules, the classical Cadherins, to control formation of muscle. To do this we have examined muscle formation within embryos of the zebrafish, a small embryologically accessible fresh water fish. We have determined how different cadherin molecules co-ordinate the final pattern of the myotome, the structure that gives rise to the majority of muscle in the early embryo. We have determined that differential cell adhesion drives cell sorting of specific muscle cell types via differential use of members of the classical cadherin family of proteins. This study aims to look further at the way that these proteins are regulated in different muscle cells of the forming body. By understanding how these molecules regulate cell sorting and adhesion within the zebrafish myotome we hope to be able to apply this knowledge to how these molecules control the formation of more complex tissues. Furthermore, we believe the implication of specific signalling pathways in the control of cadherin gene expression has particular implications for the role these proteins play in the progression of metastatic cancer.Read moreRead less