Chapter 16. Cell Signaling. Chapter 16. Cell Signaling. Chapter 16. Cell Signaling

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1 1 D. discoideum/ D. mucoroides species specific sorting. (D. discoideum: green, D. mucoroides: red)

2 Importance of cell signaling Multicellular organisms Growth and development Physiological responses Unicellular organisms Response to environment Signaling between organisms 4 An important principle: signal transduction. A signal is often changed from one physical form to another during a response. 5 Fig There are multiple types of signaling processes. 6 Fig

3 Of these, the contact dependent cell signaling is the hardest to study. Example: control of Fig nerve cell production. 7 Cell signaling by secreted molecules. Two aspects of signaling by secreted molecules The production of signals. (Basically already considered.) The response to cell signaling. We (and cell biologists generally) will focus on the response part. This also allows us to include responses that do not really involve cell to cell communication, like response of photoreceptor cells in the eye to light. 8 General features of cell signaling. The importance of receptors. Bind signal or intermediate with high specificity and affinity. (Includes some of the highest binding constants in biology) Signal binding activates receptors. Activated receptors cause change. 9 3

4 General features of cell signaling. Cells will not respond to a signal if they do not have a receptor. Cells with receptors for a given signal may not always respond the same way. (Fig. 16-5) Fig General features of cell signaling. Cells typically respond to combinations of signals. 12 Fig

5 General features of cell signaling. 13 Often there are multiple steps A signaling cascade Fig General features of cell signaling. The importance of signaling cascades. The 5 critical roles of the signaling cascades. Transfer the signal (usually across the membrane). Transform the signal (into a useful form). Amplify the signal. Distribute the signal (branching). Modulate (control) the pathway by other factors Fig

6 Fast and slow cellular responses to signals. 16 Fig As we shall see some signaling processes work primarily by turning on or off important pre-existing proteins in the cell, some work by changing the protein composition of the cell and some signaling processes do both at the same time. 17 The two major divisions of cell signaling. 18 Signaling by hydrophilic molecules. Signaling by hydrophobic molecules. There are substantial differences in between these two. Fig

7 Cell Signaling by hydrophobic signals The most well understood hydrophobic signals: the steroid hormones. 19 Fig Cell Signaling by hydrophobic signals The normal mode of action is illustrated by cortisol. (Fig ) 20 Fig Cell Signaling by hydrophobic signals This process is relatively slow. Changes can be permanent, example growth hormones, sex hormones. 21 7

8 Cell Signaling by hydrophobic signals Sometimes a steroid can generate a secondary response. Here the product of the gene that is turned on by the primary response is a protein that can in turn activate another set of genes, and result in a whole host of new proteins being made. 22 Cell Signaling by hydrophobic signals Although the concept of a signaling cascade is most applicable to the hydrophilic signal pathways we will consider shortly. Consider how the steroid signaling pathway also shows many of the features of such cascades from pg 539 of your text (fig. 16-8). 23 Cell Signaling by hydrophobic signals An interesting question: testosterone has multiple effects on different cells and organs. Are there multiple testosterone receptors? 24 8

9 Cell Signaling by hydrophobic signals A somewhat bizarre example of a membrane permeable signaling pathway NO. Fig Cell Signaling by hydrophobic signals Typically NO relaxes smooth muscle cells of blood vessel. Nitroglycerine can be metabolized to form NO. Reason for heart pills Viagra works via this pathway. In this pathway, NO leads to an increase in cgmp. Viagra inhibits the degradation of cgmp, and thus amplifies the effect of NO. 26 Fig Cell Signaling by hydrophilic signals Hydrophilic signals, cannot diffuse across the membrane. Therefore the original signal binds to a plasma membrane bound receptor and activates it. There are 3 major groups of such receptors. (Fig 16-14) 27 9

10 28 Fig Fig Fig

11 Cell Signaling by Ion-channel-linked receptors Ion-channel-linked receptors are most important in electrically active cells (nerve and muscle). For the most part, just put together stuff you already know. 31 Fig Cell Signaling by G-protein-linked receptors The structure of the G-protein receptors. 32 Fig Cell Signaling by G-protein-linked receptors Mechanism of action (c.f. Fig 16.17, ) 33 11

12 Cell Signaling by G-protein-linked receptors What does the target protein do? Possibility #1 -- modifies channel proteins 34 Fig Cell Signaling by G-protein-linked receptors What does the target protein do? Possibility #2 -- modifies enzyme activity 35 Fig Cell Signaling by G-protein-linked receptors The concept of secondary (intracellular) messengers. Messenger generated inside of the cell. Blocking a secondary messenger, prevents a cellular response even in the presence of the hormone. Adding the secondary messenger to a cell will mimic the addition of the hormone