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Chemical messengers and hormones are stored in cells in membrane bound vesicles. The contents of vesicles is released into the extracellular medium upon the fusion of the vesicle membrane with the plasma membrane, a process termed exocytosis. In many cells a stimulus is required to trigger exocytosis (regulated exocytosis), while in others exocytosis proceeds in a continuous fashion (constitutive exocytosis).
Practically all cells in human body perform a form of exocytosis. In some cells, such as neurons and endocrine cells, this process is particularly specialized. However, it is also present in adipocytes, cardiomiocytes, immune cells, photoreceptors, glial cells, plant cells and other cell types. Although exocytosis is an ubiquitous process of all eukaryotic cells, the molecular mechanisms regulating it are still unclear. In the last decade many proteins have been discovered to play a role in exocytosis, but the exact order and nature of their interactions underlying regulated exocytosis is unclear. On one side it has been hypothesized that a common molecular mechanism is essential for regulated exocytosis, but the interaction of other molecules with the essential set of molecules contribute to specific functional requirements. On the other side it has been proposed that regulated exocytosis is explained by a sequential molecular model, which states that all vesicles in a cell must undergo a sequence of events in order to fuse with plasma membrane.
To test these hypotheses, we study secretory activity in a number of model cell types, especially in pituitary cells from the anterior and intermediate lobes, which secrete prolactin, beta-endorphin and alpha-melanocyte stimulating hormone. These hormones are involved in the bodily response to stress, regulate the immune system, body temperature, body weight and other functions. In adition to this we also study the physiology of mitochondria, secretory activity of single astrocytes, adipocytes, skeletal muscle fibres and other cells.
Membrane fusion is an important process also in cell maturation, such as in the formation of skeletal muscle fibres. It also represents a key step in the production of hybrid cells used in the production of monoclonal antibodies and for the preparation of hybrid cells in immunotherapy of cancer. In these applications membranes of two adjacent cells fuse to form one cell-hybrid. In case of immunotherapy the fusion of dendritic cells with tumor cells enables the hybrid to retain properties of antigen presenting cells, but is presenting tumour antigens to other immune cells at the same time.
The aim of the "Cell Physiology" programme is therefore on one side to understand the fundamental properties of membrane fusion under physiological and pathological conditions, and on the other side to utilize this knowledge in developing hybrid cells and cell therapy related products.
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