CHAPTER 9: CELL-CELL INTERACTIONS WHERE DOES IT ALL FIT IN? Chapter 9 combines the information in Chapters 4 and 5 to provide a story about cellular interactions. These interactions are essential for understanding the signaling that controls gene expression. In addition, cell-cell interactions determine the success of multicellularity and promote the development of a fertilized egg into a normal embryo. This information should be reviewed when covering later chapters that cover cell signaling, embryology, endocrine system, and nervous system. SYNOPSIS Cells of multicellular organisms must communicate with one another so that they behave as a coordinated group of cells rather than just a bunch of independent ones. Recall the cliche “the left hand doesn’t know what the right hand is doing.” The signals to which a cell responds are dependent on the kinds of receptor proteins associated with that cell. If the signal is just the right molecular shape, it and the receptor bind eliciting a response somewhere in the cell. There are four main types of cell signaling. Direct contact and paracrine signaling are important in early organismal development. Endocrine signaling via hormones provides widespread response in both plants and animals. Synaptic signaling found in animal nervous systems produces more localized responses at the chemical synapse between the neuron and the receptor cell. Intracellular receptors are small molecules that are able to pass through the plasma membrane of the target cell. Nitrous oxide is one example. It activates the enzyme that catalyzes synthesis of cyclic GMP. A superfamily of steroid hormone receptors have specific DNA binding sites normally occupied by an inhibitory protein. When the signal molecule binds to another site on the receptor the inhibitor is released. The receptor then binds to DNA to activate or suppress a certain gene. There are three superfamilies of cell surface receptors. The signals associated with these receptors bind to receptor proteins on the cell surface. Thus an extracellular signal is converted to an intracellular signal. In chemically-gated ion channels the receptor is a transmembrane protein that winds back and forth through the membrane several times (called a multi-pass protein). The center of this protein forms a channel through which specific ions can pass. Enzymatic receptors are linked to enzymes or themselves act as enzymes. Most of these are protein kinases; they add phosphate groups to proteins. They are single pass transmembrane proteins where the region that binds with the signal molecule is located outside the cell and the portion that initiates enzymatic activity is found within it. G protein-linked receptors are sevenpass transmembrane proteins that become activated when they bind to GTP. These receptors are important because they provide the mechanism of action for over half of the therapeutic drugs currently in use. Second messengers are small molecules or ions that alter the shape and behavior of receptor proteins to relay the signal message to enzymes or genes within a cell. cAMP is the most widely used second messenger in animal cells. Ultimately the cAMP binds to A-kinase, activating it to phosphorylate certain cell proteins. Calcium is normally sequestered outside a cell or within its 48 endoplasmic reticulum. With the proper G protein signal inositol triphosphate is eventually produced, which opens calcium channels in the ER membrane. This influx of calcium triggers many activities. In most cases, a cellular signal is too insignificant to result in an adequate cellular response. Protein kinase cascades amplify the signal. In vision for example, a single light-activated rhodopsin molecule activates many transducin molecules that further split 105 cyclic GMP molecules. The expression of cell identity results from the presence of unique cell surface markers, some of these, like those associated with ABO blood types, are glycolipids. Others are proteins anchored in the plasma membrane — the major histocompatibility complex (MHC) proteins, for example. Cells in a multicellular organism establish physical connections whereby sheets are created to form walls and partitions. Tight junctions are an example of these within an animal’s digestive tract. Anchoring junctions are common in tissues exposed to stress. In cadherin junctions, desmosomes for example, a cell’s cytoskeleton is attached to that of other cells or to the extracellular matrix. Adherens junctions connect actin filaments of cells via linking proteins called integrins. Communicating junctions, gap junctions in animals, and plasmodesmata in plants, allow the passage of ions or molecules from one cell to another. LEARNING OUTCOMES Know what receptor proteins are, where they are located, and what they do. Describe the four types of cell signaling. Differentiate between intracellular receptors and cell surface receptors in terms of function. Know the three cell surface receptor superfamilies, the basic structures of each and how each functions to convert an extracellular signal to an internal one. Understand how cAMP and calcium function as second messengers and why they are necessary. Explain the amplification process associated with protein kinase cascades. Know what cell surface markers are, where they are located, and give examples. Describe the three primary kinds of junctions that exist between cells. Compare and contrast communicating junctions, gap junctions, and plasmodesmata. 49 COMMON STUDENT MISCONCEPTIONS There is ample evidence in the educational literature that student misconceptions of information will inhibit the learning of concepts related to the misinformation. The following concepts covered in Chapter 9 are commonly the subject of student misconceptions. This information on “bioliteracy” was collected from faculty and the science education literature. The lipid layer is a solid surface Cell membrane proteins are immoveable in the bilayer Only hormones are cell signals All hormones are related to steroids Desmosomes are the same as plasmodesmata Plant cells are completely isolated from each other and make no cell contact Plants do not produce hormones Cells make direct contact with each other’s lipid bilayer Neurotransmitter receptors are not the same as hormone receptors All hormones act on cell surface receptors Cell surface receptors are not associated with changes in gene expression INSTRUCTIONAL STRATEGY PRESENTATION ASSISTANCE Students need to be secure in the material from the previous chapter to progress in this one. There is a lot of new terminology. Flash cards will help the students learn this information — making them as much as using them. Table9.2 is an invaluable summary of the chapter, but too many students will use it as a crutch and just memorize it. It’s much better if they make their own table(s). The best part of the learning process is in the organization and gathering of information. Re-emphasize the importance of molecular binding to induce three-dimensional shape changes to effect a variety of changes within the cell. Stress the importance of protein kinases. The topic will come up again in gene expression and regulation. It’s amazing how a simple addition of a PO4 group can do so much in a cell! Don’t let your students confuse desmosomes and plasmodesmata. They sound similar, but are very different structures. HIGHER LEVEL ASSESSMENT Higher level assessment measures a student’s ability to use terms and concepts learned from the lecture and the textbook. A complete understanding of biology content provides students with the tools to synthesize new hypotheses and knowledge using the facts they have learned. The following table provides examples of assessing a student’s ability to apply, analyze, synthesize, and evaluate information from Chapter 9. 50 Application Analysis Synthesis Evaluation Have students predict would happen if a chemical that blocks cAMP were given to a culture of cells. Ask students to determine the chemical nature of a hormone that affects a cell in spite of the presence of cell surface receptors for the hormone.. Ask students to explain why insufficient calcium in the tissues affects cell interactions. Ask students describe the properties of a chemical that blocks an intracellular receptor. Have students explain how cell to cell communication will be affected by bathing cells in a solution of enzymes that degrade proteins. Ask students explain why certain organisms that enter cells can only invade specific cells in an organism. Ask students come up with uses of a drug that inhibits the action of protein kinases in targeted cells. Ask students to come up with commercial and food preparation uses for fungi known to degrade cell junction proteins. Ask students to explain how genetic modification techniques that alter Gprotein function can be used to produce new types of agricultural animalss. Ask students to compare and contrast the cell surface receptors to proteins involved in active transport. Ask students to evaluate a claim about a drug that increases alertness because it supplies phosphorus that fuels kinases of the brain cells. Have students explain the validity of using oral ATP supplements to enhance cell signaling. VISUAL RESOURCES 1. The amplification analogy in the book is very straight forward, but students will quickly identify with the shampoo commercial where “you tell two friends and they tell two friends ... while they see on TV one person, then two, then four, and so on. You could 51 also do a class demo on this, distributing note cards, rubber bands, or other small, inexpensive objects. 2. Make models of various cell–cell interactions using plastic, paper, string, straws, etc. Better yet, have your students make them, collect them, choose the best, and you will have models to show in class next semester! IN-CLASS CONCEPTUAL DEMONSTRATIONS A. Cell Signaling Role Playing Introduction Molecular role playing is a fun and effective way to demonstrate complex concepts to students. This activity asks students to demonstrate the differences between cell communication systems. Use this activity to help students summarize and review the events of cell signaling. Materials Colored markers Sheets of 8 ½” X 11” white paper Students volunteers 2 15’ sections of rope of twine Scissors 10 feet of thick tubing Ample space to move around Procedure and Inquiry 1. Tell students that they are to plan a play in which they will be role modeling the mechanisms of cell to cell communication. 2. Ask them to use the rope to represent the cell membrane of an individual cell, the tubing to depict a blood vessel, and each student will represent a cell structure involved in cell signaling. They must use the marker and paper to label the role of each individual who is demonstrating a cell signaling structure. 3. First, instruct the students to role play the four basic mechanisms of cell communication: direct contact, paracrine signaling, endocrine signaling, or synaptic signaling. 4. Have the students discuss the accuracy of their role model. 5. Next, ask the students to role play intracellular receptor cell signaling. 6. Have the students discuss the accuracy of their role model. 7. Then, ask the students to role play cell surface receptor cell signaling. 8. Have the students discuss the accuracy of their role model. 9. Recap the activity by asking how such demonstrations may be useful for researchers investigating cell signaling mechanisms. B. Building Cell Junction Models 52 Introduction Molecular modeling using household materials was one of the techniques used by Watson and Crick as they were deciphering the structure of DNA. This activity asks students to models of cell junctions using common household materials provided to them. Use this activity to help students reinforce and review the structure and function of cell junctions. . Materials Colored markers Sheets of 8 ½” X 11” white paper Students volunteers divided into teams or work groups Color pipe cleaners Modeling or craft clay Scissors Fish tank tubing or laboratory hosing Ample table space to do the construction Double sided cellophane or carpet tape Clear cellophane tape Procedure and Inquiry 1. Tell students they will work in teams to use the materials given to them to represent the different types of cell junctions taught in class. 2. They cannot use the book, Internet, or other resources to design the junctions. 3. Have students divided into teams that will construct one type of cell junction. Large classes can have multiple groups produce junctions so the class can compare the models. 4. Students should be asked to model the following junctions: a. Desmosome b. Hemidesmosome c. Tight junction d. Gap junction e. Plasmodesmata f. Adherens junctions 5. Have the students discuss the accuracy of their models. 6. Recap the activity by asking how models may be useful for researchers investigating cell structure. USEFUL INTERNET RESOURCES 1. Case studies are excellent for reinforcing scientific concepts. The University of Buffalo produced a study called “Taking It on the Chin: A Case Study on the Nervous System” addresses cell communication related to illness. It has students investigate signaling programs related to nervous system function. This case study can be done in class or be given as a take-home. The case study can be found at http://www.sciencecases.org/chin/chin_notes.asp. 53 2. Case studies introduce real-world applications of biological principles. This case study developed for the University of Buffalo called “Gender: In the Genes or in the Jeans?” to give students an understanding of cell signaling and other factors related to gender development. This is an excellent case study for uncovering the myths associated with the biology of gender. The case study is available at http://www.sciencecases.org/gender/gender.asp. 3. Undergraduate students are rarely exposed to the specilized research involved in building the conceptual foundations of biology textbooks. Students can be show the different types of cell signaling research being done by visiting the “Signaling Gateway” website hosted by the Association of Learned and Professional Society Publishers. The website can be found at http://www.signaling-gateway.org/. 4. Animations used during lecture are great for reinforcing abstract concepts such as cell signaling. Supplement a cell signaling lecture using Flash animations available on the Gallery of Cell Signaling website. The website can be found at http://www.celanphy.science.ru.nl/Bruce%20web/Flash%20Movies.htm. LABORATORY IDEAS A. Response to Cell Signals a. Have students investigate the signaling response of an animal model to adrenalin. b. This laboratory activity looks at the effect of adrenalin as a signal that affects the metabolic rate of particular cells. c. Provide students with the following materials: i. Daphnia kept in a container of clean fresh water ii. A large container of clean water for used daphnia iii. Droppers for collecting and transporting the daphnia iv. Microscope v. Microscope slides per observation vi. Droppers for transporting chemicals vii. Over-the-counter epinephrine preparation (asthma pills) soaked in 100ml of a 50% ethyl alchohol/50% water mixture viii. Surgical gloves and goggles d. Have the students carry out the following procedure: i. Ask the students to place some daphnia on the microscope slide and observe their normal behavior ii. Make sure they keep adding water to the slide to keep the daphnia from drying out and dying iii. Have them keep track of the speed at which they are moving around how fast they move their feet. iv. Then have the students add one drop of the epinephrine solution to the daphnia v. The students should note what happens to movement of the daphnia vi. Have the students repeat steps iv and v several times 54 vii. Students should then be asked to investigate how adrenalin works as a cell signal and whether their observations were consistent with findings on other organisms viii. Ask students to investigate the types of cells and tissues in the daphnia that are response to the adrenalin B. Comparative Response to Cell Signals a. Have students investigate the specificity of cell signaling responses of an animal and a plant. b. This laboratory activity looks at the differential effects of caffeine and adrenalin as a signal that may or may not affect the metabolic rate of cells. c. Provide students with the following materials: i. Daphnia kept in a container of clean fresh water ii. Elodea kept in a container of clean fresh water iii. Droppers for collecting and transporting the daphnia iv. Forceps for transporting the elodea v. Microscope vi. Droppers for collecting samples of epinephrine and caffeine vii. 2 clean microscope slides per observation viii. Over-the-counter epinephrine preparation (asthma pills) soaked in 100ml of a 50% ethyl alchohol/50% water mixture ix. 100mg caffeine pill soaked in 100ml of a 50% ethyl alchohol/50% water mixture x. Surgical gloves and goggles d. Have the students carry out the following procedure: i. Ask the students to place some daphnia and elodea on the same microscope slide ii. Observe their normal behavior and the cytoplasmic streaming of the elodea iii. Make sure the students keep adding water to the slide to keep the daphnia and elodea from drying out and dying iv. Have them keep track of the speed at which the daphnia and the cytoplasmic are moving. v. Then have the students add two drops of the epinephrine solution to the slide vi. The students should note what happens to the daphnia and the elodea vii. Next, ask the students to place some daphnia and elodea together on a new microscope slide viii. Then have the students add two drops of the caffeine solution to the slide ix. The students should note what happens to the daphnia and the elodea x. Students should then be asked to investigate the effects of adrenalin and caffeine on the cells. They should use the Internet or other resources to see how each works as a cell signal. 55 LEARNING THROUGH SERVICE Service learning is a strategy of teaching, learning and reflective assessment that merges the academic curriculum with meaningful community service. As a teaching methodology, it falls under the category of experiential education. It is a way students can carry out volunteer projects in the community for public agencies, nonprofit agencies, civic groups, charitable organizations, and governmental organizations. It encourages critical thinking and reinforces many of the concepts learned in a course. Students who have successfully mastered the content of Chapter 9 can apply their knowledge for service learning activities in the following ways: 1. Have students talk to youth sports groups about how steroids affect cell function. 2. Have students design an electronic animated presentation on cell signaling for teachers at local schools. 3. Have students tutor middle school or high school biology students studying cell function. 4. Have students talk to the elderly about “youth drugs” that rely on cell signaling such as growth hormone or estrogens. 56