CELL SIGNALLING (cell signaling) British vs. Amer. English • Why does CELL SIGNALLING exist in nature? All cells receive and respond to signals from their surroundings. Even the simplest bacteria sense and swim toward high concentrations of nutrients, such as glucose or amino acids. Many unicellular eukaryotes also respond to signaling molecules secreted by other cells, allowing cell-cell communication. Mating between yeast cells, for example, is signaled by peptides that are secreted by one cell and bind to receptors on the surface of another. It is in multicellular organisms, however, that cell-cell communication reaches its highest level of sophistication. Whereas the cells of prokaryotes and unicellular eukaryotes are largely autonomous, the behavior of each individual cell in multicellular plants and animals must be carefully regulated to meet the needs of the organism as a whole. This is accomplished by a variety of signaling molecules that are secreted or expressed on the surface of one cell and bind to receptors expressed by other cells, thereby integrating and coordinating the functions of the many individual cells that make up organisms as complex as human beings. • The binding of most signaling molecules to their receptors initiates a series of intracellular reactions that regulate all aspects of cell behavior, including metabolism, movement, proliferation, survival, and differentiation. Understanding the molecular mechanisms responsible for these pathways of cell signaling has thus become a major area of active research (important for cytostatic and other anti-cancer drug, regeneration, anti-apoptotic drug, …). Rule 2 Rule 3 Learn the scheme!!! 1) 2) 3) 4) 5 5) …and very specific JUXTARINE cell-to-cell signaling type of cell–cell or cell–extracellular matrix signaling in multicellular organisms that requires close contact. There are three subtypes: A B C A = communicating junction links the intracellular compartments of two adjacent cells, allowing transit of relatively small molecules. B = membrane ligand (protein, oligosaccharide, lipid) and a membrane protein of two adjacent cells interact. C = ExtraCellular matrix (ECM) such as glycoprotein and a membrane protein interact Additionally, in unicellular organisms such as bacteria, juxtacrine signaling means interactions by membrane contact. Juxtacrine signaling has been observed for some growth factors, cytokine and chemokine cellular signals, playing an important role in the immune response. Mechanism of singaling Overview – signal net Most important signal molecules in clinical pharmacology and experimental biology. Please, learn minimaly 5 hormones and 5 local mediatores And 2 neurotransmiter (Name Chemical nature Action) Signaling is important for a) CELL CYCLE b) APOPTOSIS c) NON-apoptotic death • (note: necrosis is very fast and unprogramed death, where injury or toxic enviroment prevent apoptosis or another non-apoptotic death, cell is lysed and solution is dangerous for near cells in tissue) a) Cell cycle b) Apoptosis apoptosis - microscopical view to tissue Example of apoptosis in rat heart (infarction of myocardium) Apoptitc staining Control • Figure 5C illustrates cleaved caspase-3 staining for apoptosis revealing the presence of intracytoplasmic positive myofibers (small arrows) located in the interventricular septum; large arrow indicates an apoptotic body. Figure 5D is a negative control of the same heart demonstrated in 5C. The small arrows demonstrate degenerating myofibers; large arrows indicate apoptotic bodies. (note: This proteolytic cascade, in which one caspase can activate other caspases, amplifies the apoptotic signaling pathway and thus leads to rapid cell death ) apoptosis Some advanced article for future study (not in exam) (apoptosis is important curative factro in ancer, infarcted region, neurodageneratie d.) Inhibiting the inhibitors: Targeting anti-apoptotic proteins in cancer and therapy resistance Nir Shahar 1, Sarit Larisch 2 Abstract The cytotoxic effect of anti-cancer drugs relies on their ability to induce programmed cell death known as apoptosis. Evading apoptosis is a common characteristic of cancer cells and it is linked to both carcinogenesis and anticancer drug resistance. Revisiting miRNA-21 as a Therapeutic Strategy for Myocardial Infarction: A Systematic Review V Sothivelr, MY Hasan, S Mohd Saffian… - Journal of …, 2022 Studies described thecardioprotective effects of miR-21 to reduce infarct size by improving angiogenesis, antiapoptotic... An overview of investigational antiapoptotic drugs with potential application for the treatment of neurodegenerative disorders A. Camins, F. Sureda, +4 authors M. Pallàs, 2010 c) NON-apoptotic death (learn minimaly 5 death-names and 5 initial signal molecule) Advanced publication: