Cell-cell communication. Cell-cell communication is distancedependent 8/20/13

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1 Cell-cell communication With over 75 trillion cells in the human body, we need to understand how cells communicate with one another. The two primary ways that cells communicate are either by electrical signals or chemical signals. We will look at both in this section of the course. Before we dive into this in too much detail, we want to look at general trends in communication. Cell-cell communication is distancedependent You might communicate with someone differently depending on how far they are from you (next to you versus across the ocean, for instance). To some extent, cells are the same way. Cell-cell communication is distancedependent 1. Gap Junctions Cells that are right next to one another can communicate via protein channels that directly link them together. These proteins are called connexin proteins, and the channels that are produced are called connexons. These connexons can open or close (and do so under a variety of cues); multiple things can pass through them (only way for electrical signals to pass directly from cell-cell). Also when they are open, they these tissues like one cell with multiple nuclei (a syncytium). What s a cell that occurs without gap junctions that s a syncytium? 1

2 Cell-cell communication is distancedependent 2. Contact-dependent signals Requires that cells are in direct contact with one another. Common during growth and development, as well as in the immune system (think about antigen presentation, etc). Cell-adhesion molecules (CAMs) often play a role in contact-dependent signaling Cell-cell communication is distancedependent 3. Autocrine & Paracrine signaling A chemical is released into the local environment, affecting only the nearby, surrounding, cells. The biggest difference between autocrine and paracrine signaling is the cell that responds to the signal: If the cell that released the signal responds to it, this is autocrine (auto = self); the cell is essentially activating itself. If a nearby cell responds to the signal, this is paracrine. 2

3 Cell-cell communication is distancedependent Everything we ve talked about so far deals with cells that are close to one another. Also, we ve only talked about chemical signals. What about cells that are long distances from each other? Long-distance communication can be either electrical or chemical. The endocrine system uses hormones to send messages over long distances The nervous system uses both chemical and electrical signals to send messages. Neurocrines are the chemicals released by nervous system cells, and can be classified as neurotransmitters, neurohormones, or neuromodulators. Response to chemical signals There are two questions to be addressed here: 1. What causes some cells to respond to a signal, and some to ignore it? 2. If a cell does respond to a signal, how does it respond? The proteins found on the surface of the cell differ from cell-cell (what do you think causes the difference?) Some of the proteins found on the cell membrane or within the cell bind to signaling molecules. A cell can only respond to a signal if it has the proper receptor protein. 3

4 Response to chemical signals There are two questions to be addressed here: 1. What causes some cells to respond to a signal, and some to ignore it? The cell must have the proper receptor protein, either on its membrane, or in the cytosol/nucleus 2. If a cell does respond to a signal, how does it respond? If a cell does respond to a signal, how does it respond? The answer depends on whether the signaling molecule is lipophilic or lipophobic. Lipophilic molecules can diffuse through the cell membrane; lipophobic molecules cannot. Lipophobic molecules tend to act on existing proteins, thus they have fast response time (ms to min) Lipophilic molecules bind receptors either (a) in the cytosol, or (b) in the nucleus. This messengerreceptor complex acts as a transcription factor, and results in initiation of transcription. This either causes genes to be turned on or off. Effects are slower to see (can be hours). 4

5 vs. These are less common, but still very important to our physiology Response times of minutes to hours Results in transcriptions of new proteins. Binds receptors in cytosol or nucleus 5

6 Signal transduction Both receptor-enzymes and G-protein coupled receptors use second messengers learn to recognize names like camp, IP 3, and DAG as second messengers Protein kinases are also important in phosphorylating or dephosphorylating proteins where do you think that phosphate might come from? But, other signaling molecules, like calcium, are extremely important in physiology (we ll see calcium all the time this semester). Turning the signal off In order to maintain homeostasis, these signals cannot be turned on forever; they must be turned off at some point. Homeostasis is regulated largely by reflex pathways, which have two loops: response loops feedback loops 6

7 S-mulus Sensor Feedback Loop Input Signal Response Loop Integra-ng Center Output Signal Target Response 7

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9 Negative feedback loops Negative feedback loops are homeostatic They stabilize the variable within the normal range of function They restore the normal state 9

10 Physiological setpoints can be changed either by acclimation (done artificially in a lab) or by acclimatization (done naturally). Postive feedback loops: Are NOT homeostatic The response must be stopped by some outside factor (in this example, the delivery of the baby) Other examples include the milk letdown reflex during breastfeeding 10

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12 Here, the effect is not addi-ve, but rather mul-plica-ve. One hormone seems to poten-ate the others. This is the concept of hormonal synergism. Hormones also commonly work antagonis-cally to one another, where one hormone negates (or balances) the effects of another. Insulin and glucagon are two really good examples of antagonis-c hormones. 12