Laith Abu Shekha. Omar Sami. Ebaa Alzayadneh

Transcription

1 24 Laith Abu Shekha Omar Sami Ebaa Alzayadneh

2 Signal Transduction Please note that it s very important to refer to the slides. Introduction: Through these five lectures, we should know the basics of signal transduction. Cellular Signaling: which is cell-cell communication via signals. Signal transduction: Process of converting extracellular signals into intra-cellular responses. But why is it called transduction? Well, it is usually across the plasma membrane so it is called transduction, it is like if we have a barrier between ICF & ECF and we need something to transduce the signal across the membrane. Note that: A lot of aspects of cellular functions can be altered by cellular signaling. In other words signal transduction is a science of understanding how individual cells sense and interact with their environment and respond to the stimuli of the environment. Question: How so many functionally different cells can arrive from one fertilized ovum? Answer: The answer is: signaling between cells which tell each cell to which type it should differentiate; so this is only one example of cell signaling. A few examples of different types of cells can arrive from fertilized ovum: The first example, when you have food the cell can interact with the environment(food), around this type of cell so it can reacts with oxygen levels, sugar presence as well as temperature, so those are stimuli from the environment that can affect by signaling the cellular processes that take place inside the cells. The second example signals they can create different cell types and this is the differentiation example so depending on signals that comes to the cell it can tell the cell to which type of cells it should differentiate. 1 P a g e

3 Note: that signals may also have an inhibitory effect; for example, sometimes signals may inhibit certain functions of the cell like inhibiting differentiation or duplication and so on. There are so many signals that integrate or affect the cell function so at one time there might be thousands of signals that affect the cell, but the integration of all these signals will cause the cell to differentiate into a specific type of cells. Ligand: the signaling molecule, or any molecule that can bind to its specific receptor in order to transfer a signal. Receptors: Bind specific ligand, Transmit signals to intracellular targets. Different receptors can respond differently to the same ligand. Notice that: the receptor is usually a protein or a glycoprotein that could be found in the plasma membrane, the cytoplasm, on the nuclear membrane or even inside the nucleus. Components involved in signaling Ligands Receptors Intracellular Signaling Proteins Inactivating Proteins Intermediary Proteins Target Proteins Enzymes Second Messengers - Signaling or communication by extra cellular signaling involves certain steps, let s have a closer look! 1- Synthesis of signaling molecule which in turn will act as a signal. 2 P a g e

4 However, there is no specific signaling molecule that will bind to the receptors to make a signal for the cell, which means that the signaling molecules may differ; it can be a gas like oxygen or even a physical stimulus like pressure, light or heat which cause conformational change to the receptors. Note that: In case of light, heat or pressure NO signaling molecules are needed 2- releasing of signaling molecule: Signaling molecules are released by the signaling cells then it s the time to transport the signal into the target cell. 3-binding of the signal with a specific receptor: But first let us know more about the word Receptor The main function of the receptor is to transport the signal from ECF to ICF (but it may be present on the intracellular side and the ligand can cross the plasma membrane and bind to the receptor). Note: The receptor is NOT always on the plasma membrane, yet it depends if the receptor is soluble in lipids or not. Let us continue step3: when the signal is on the membrane the molecule will bind with the receptor and enter the membrane, after binding; Signal transduction pathway will start, and this will lead to various changes inside the cell; Changes are various (phosphorylation, dephosphorylation, chemical changes that change the function or moves the protein to bind to Another protein) the change may cause alteration of activity of enzymes (might be excited or inhibited) *** Again remember that the signaling molecule has both inhibitory & stimulatory effect. After the ligand caused an alteration to the cell, it is the time to leave the receptor; many termination steps occur to deactivate the ligand. The picture below helps us to recall all what we have mentioned earlier 3 P a g e

5 So far I guess it is obvious that all of us know the following: The same signal can produce different responses in different types of cells, for example epinephrine which leaves the adrenal medulla to bind with a receptor; this receptor mat be either in cardio myocytes, and in turn the contraction will increase OR it may bind to the sinoatrial node and it will increase the heart rate. Remember: 1- Signals get translated into cellular responses or changes in gene expression. 2- Not all receptors should be bound to their ligands to cause a physiological response. 3- Different combination of signals induce different responses. Responses can be fast or slow; the difference between the two types of responses is that the fast one doesn t need gene transcription and protein synthesis because these processes take a long time to happen. It is important to note that: it is not essential to saturate all receptors to produce maximum phsylogical response. Let us have a closer look at the picture below 4 P a g e

6 Small amount of ligand may be able to induce a big response. To reach half of the maximum response we need one fourth of the relative concentration of ligand. Types of signaling between cells: 1) Paracrine: ligand can bind to a nearby cell via interstitial fluid. 2) Autocrine: If it binds to a receptor on the same cell. Notice that: 1- Autocrine is considered to be locally mediated as it only acts on the same signaling cell. 2- Autocrine is involved in negative feedback mechanisms. 3) Endocrine: If the ligand is secreted into blood and then transported into another location such as hormone which act on distant target cells. 4) Synaptic: The changes may be very fast or slow. Neurotransmitters bind on postsynaptic cell in response to an electrical stimulus. 5 P a g e

7 Note: Autocrine is locally mediated. - If we need to change the genetic expression, it will take a long time - If we changed the function of a protein, enzymatic activity or membrane potential, it might be very fast. Amplification of signal: A huge number of proteins will be affected and they will affect other proteins. 6 P a g e

8 When a neuron secrets neurotransmitters from the bulb of axon terminal, these neurotransmitters affect other cells, it can happen between neural cell and muscle cell. Notice that Neurotransmitters can be secreted into blood to other organs; for example: Epinephrine is secreted from adrenal medulla. Antidiuretic hormone also is synthesized from hypothalamic neurons and then transported through neuron axons into the posterior pituitary gland, specifically to the posterior lobe and then secreted into the blood stream. Chemical classification and functions of hormones: Endocrine Hormones: 1. Amino acid derivatives: like epinephrine and norepinephrine, both of them are derived from tyrosine, and their function is stress responses, these hormones are stimulated by autonomic nervous system when something dangerous happens, so it increase the heart rate, blood pressure and produces glucose to help the body in case of danger. 2. Peptides: They are smaller than proteins, for example Antidiuretic hormone, hypothalamic hormones and thyroxin which is derived from tyrosine. 3. Proteins: like anterior pituitary hormones, which its function is regulating of other endocrine systems. 4. Steroids: like sex hormones (androgens and estrogens) and corticosteroids, they can easily cross the plasma membrane without any necessary required membrane bound receptors but it doesn t mean that there are no receptors. Paracrine Hormones: 1. Amino acid derivatives: like histamine which is a local mediator can make vasodilation for the blood vessels. 2. Arachidonic acid derivatives: like prostaglandins The function of paracrine hormones is local responses to stress and injury. 7 P a g e

9 See the figure below for better explanation Medicine is only for those who cannot imagine doing anything else. 8 P a g e