BIOLOGY I

Chapter 11: CELL COMMUNICATION Evelyn I. Milian Instructor 2012

BIOLOGY I. Chapter 11 – Cell Communication

Why is cell-to-cell communication important? • Communication between cells is important for multicellular organisms as well as for unicellular organisms. • Cells communicate with each other to coordinate their activities in a way that enables an organism to develop, survive and reproduce. – Share nutrients, ions, etc. – Influence other cells through signals – Interact to work together in tissues and organs (e.g. the heart, the muscles) Evelyn I. Milian - Instructor

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BIOLOGY I. Chapter 11 – Cell Communication

Evolution of Cell Signaling • Signal transduction pathway: the process by which a signal on a cell’s surface is converted into a specific cellular response. • Cell signaling (signal transduction) in microbes (such as yeast, a type of fungus) has much in common with processes in multicellular organisms, including animals, suggesting an early origin of signaling mechanisms.

Evelyn I. Milian - Instructor

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BIOLOGY I. Chapter 11 – Cell Communication

Local and Long Distance Signaling 1. Cell communication by direct contact between cells: – Cell junctions: allow molecules to pass freely between adjacent cells. • Gap junctions, plasmodesmata, etc.

– Cell-cell recognition: cells communicate by interaction between cell surface molecules. • Very important in such processes as embryonic development and immune responses. Evelyn I. Milian - Instructor

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BIOLOGY I. Chapter 11 – Cell Communication

Local and Long Distance Signaling 2. Cell communication by indirect contact through messenger molecules: a) Paracrine signaling = local regulators released by a secreting cell travel only short distances to influence neighboring cells. • Example: growth factors.

b) Synaptic signaling = neurotransmitters released by a nerve cell stimulate a target cell. • The neurotransmitter is released into the synapse, the space between the nerve cell and its target cell.

A nerve signal can travel along a series of nerve cells, some of which can be quite long; therefore, it can also be considered long-distance signaling.

Evelyn I. Milian - Instructor

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BIOLOGY I. Chapter 11 – Cell Communication

Local and Long Distance Signaling

c) Endocrine (hormonal) signaling = chemicals called hormones are released by specialized endocrine cells into blood vessels. – The hormones may travel long distances to other parts of the body.

– Insulin, a hormone that regulates sugar levels in blood, is an example of a mammalian hormone.

Evelyn I. Milian - Instructor

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BIOLOGY I. Chapter 11 – Cell Communication

The Three Stages of Cell Signaling (Communication): Overview • From the perspective of the cell receiving the message, the process of cell signaling can be divided into three stages: Reception: The target cell’s detection of a signal molecule (ligand) from outside the cell, when it binds to a receptor protein. 2) Transduction: The conversion of a signal from outside the cell to a form that can bring about a specific cellular response. 3) Response: The change in a specific cellular activity brought about by a transduced signal from outside the cell. 1)

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BIOLOGY I. Chapter 11 – Cell Communication

Cell Signaling (Communication): (1) Reception • In reception, a signal molecule, called a ligand, binds to a receptor protein (located on the cell’s surface or inside the cell) causing it to change its shape (conformation). – * This binding is highly specific. – * Most signal receptors are plasma membrane proteins. However, some signal receptors are intracellular (located inside the cell, in the cytoplasm or the nucleus).

Evelyn I. Milian - Instructor

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BIOLOGY I. Chapter 11 – Cell Communication

Intracellular Receptors • Intracellular receptors are cytoplasmic or nuclear proteins. • Signal molecules that are small enough or hydrophobic enough and can readily cross the plasma membrane use these receptors. – Examples include: steroid hormones (such as testosterone) and thyroid hormones.

Evelyn I. Milian - Instructor

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BIOLOGY I. Chapter 11 – Cell Communication

Receptors in the Plasma Membrane • Most water-soluble signaling molecules, generally too large to pass freely through the plasma membrane, bind to specific sites on receptor proteins embedded in the plasma membrane of the cell. • The specific ligand binds to the receptor on the plasma membrane and the receptor either changes shape or aggregates.

• Three major types of plasma membrane receptors are: – G-protein-coupled receptors – Receptor tyrosine kinases – Ion channel receptors Evelyn I. Milian - Instructor

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BIOLOGY I. Chapter 11 – Cell Communication

Receptors in the Plasma Membrane: G-Protein-Coupled Receptors • A G-protein-coupled receptor is a membrane receptor that works with the help of a cytoplasmic G protein, which binds the energy-rich molecule GTP (guanosine triphosphate).

G-protein-linked receptors are widespread in organisms and diverse in their functions, including roles in sensory reception. They are also involved in many human diseases, including bacterial infections.

• Ligand binding activates the receptor, which then activates a specific G protein, which activates yet another protein, thus propagating the signal along a signal transduction pathway. Evelyn I. Milian - Instructor

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BIOLOGY I. Chapter 11 – Cell Communication

Receptors in the Plasma Membrane: Receptor Tyrosine Kinases • Receptor tyrosine kinases have enzymatic activity and react to the binding of signal molecules by forming dimers and then adding phosphate groups to tyrosines on the cytoplasmic side of the other subunit of the dimer. • Relay proteins in the cell can then be activated by binding to different phosphorylated tyrosines, allowing this receptor to trigger several pathways at once. These receptors are involved in cell growth and reproduction.

A tyrosine kinase is an enzyme that catalyzes the transfer of a phosphate group from ATP to the amino acid tyrosine on a substrate protein.

Evelyn I. Milian - Instructor

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BIOLOGY I. Chapter 11 – Cell Communication

Receptors in the Plasma Membrane: Ion Channel Receptors • A ligand-gated ion channel receptor in a membrane opens or closes when a specific signal molecule binds to the receptor protein, regulating the flow of specific ions. • These receptors have a region that can act as a “gate” when the receptor changes shape upon binding of the ligand. The gate opens or closes, allowing or blocking the flow of specific ions, such as Na+ or Ca2+ through a channel in the receptor.

Evelyn I. Milian - Instructor

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BIOLOGY I. Chapter 11 – Cell Communication

Cell Signaling (Communication): (2) Transduction • Transduction is the conversion of a signal from outside the cell to a form that can bring about a specific cellular response. – It is initiated when the binding of the signaling molecule changes the receptor protein in some way.

• Transduction often occurs through a sequence of changes requiring different relay molecules—a signal transduction pathway. – Cascades of molecular interactions relay signals from receptors to target molecules in the cell. – At each step in a pathway, the signal is transduced into a different form, commonly a conformational change in a protein.

• Advantage of multistep pathways: – Greatly amplifying a signal (and thus producing a large cellular response), more opportunities for coordination and regulation. Evelyn I. Milian - Instructor

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BIOLOGY I. Chapter 11 – Cell Communication

Cell Signaling (Communication): (2) Transduction • Phosphorylation and dephosphorylation of proteins is a widespread cellular mechanism for regulating protein activity. – Phosphorylation: The addition of a phosphate group to a protein or another molecule. • Many signal transduction pathways include “phosphorylation cascades”; a series of enzymes called protein kinases each transfer a phosphate group (from ATP) to the next protein in line, activating it.

– Dephosphorylation: The removal of a phosphate group. • Enzymes called protein phosphatases rapidly remove the phosphates from the proteins kinases, making them inactive and available for reuse (turning off the signal transduction pathway when the initial signal is no longer present). Evelyn I. Milian - Instructor

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BIOLOGY I. Chapter 11 – Cell Communication

Evelyn I. Milian - Instructor

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BIOLOGY I. Chapter 11 – Cell Communication

Cell Signaling (Communication): (2) Transduction

• Small Molecules and Ions as Second Messengers – In addition to proteins (kinases, phosphatases), signal transduction pathways may involve small nonprotein watersoluble molecules or ions called second messengers (the “first messenger” is the extracellular signal molecule that binds to the membrane receptor).

– Second messengers, diffuse readily through the cell and thus help broadcast signals quickly. – Examples: cyclic AMP (cAMP) and calcium ions (Ca2+).

Evelyn I. Milian - Instructor

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BIOLOGY I. Chapter 11 – Cell Communication

Small Molecules and Ions as Second Messengers • Cyclic AMP (cyclic adenosine monophosphate) – The first messenger activates a G-protein-linked receptor, which activates a specific G protein. – In turn, the G protein activates adenylyl cyclase, an enzyme embedded in the plasma membrane, which converts ATP to cAMP. – The cAMP then activates another protein. Evelyn I. Milian - Instructor

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BIOLOGY I. Chapter 11 – Cell Communication

Small Molecules and Ions as Second Messengers

• Calcium Ions (Ca2+) – Many signal molecules in animals (e.g. neurotransmitters, growth factors, some hormones), induce responses in their target cells via signal transduction pathways that increase the cytosolic concentration of Ca2+. This causes many responses in animal cells, such as muscle cell contraction, secretion of certain substances, and cell division. – Cells use Ca2+ as a second messenger in both G-protein and tyrosine kinase pathways. Evelyn I. Milian - Instructor

Figure 11.11. The maintenance of Ca2+ concentration in an animal cell. The Ca2+ concentration in the cytosol is usually much lower than in the extracellular fluid and ER.

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BIOLOGY I. Chapter 11 – Cell Communication

Small Molecules and Ions as Second Messengers • Calcium Ions (Ca2+) and Inositol Trisphosphate (IP3) – In response to a signal relayed by a signal transduction pathway, the cytosolic calcium level may rise, usually by a mechanism that releases Ca2+ from the cell’s endoplasmic reticulum. – Calcium release in the cell involves two other second messengers, IP3 and DAG (diacylglycerol). DAG functions as a second messenger in other pathways. Evelyn I. Milian - Instructor

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BIOLOGY I. Chapter 11 – Cell Communication

Cell Signaling (Communication): (3) Response • Signal transduction ultimately triggers a cellular response, leading to the regulation of one or more cellular activities. • Cytoplasmic and Nuclear Responses – In the cytoplasm: Enzyme activity, rearrangement of the cytoskeleton, protein synthesis, protein activity, and many other activities are regulated. – In the nucleus: Activation or inactivation of specific genes, by transcription factors (special proteins that control which genes are turned on in a particular cell at a particular time).

Evelyn I. Milian - Instructor

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BIOLOGY I. Chapter 11 – Cell Communication

Cell Signaling (Communication): (3) Response in the Cytoplasm or the Nucleus

Evelyn I. Milian - Instructor

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BIOLOGY I. Chapter 11 – Cell Communication

Cell Signaling (Communication): Fine-Tuning of the Response • Signal Amplification – One of the benefits of multistep signaling pathways is signal amplification: each catalytic protein in a signaling pathway amplifies the signal by activating multiple copies of the next component of the pathway.

• The Specificity of Cell Signaling and Coordination of the Response – The particular collection of proteins in a cell gives the cell great specificity in both the signals it detects and the responses it carries out. Evelyn I. Milian - Instructor

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BIOLOGY I. Chapter 11 – Cell Communication

Cell Signaling (Communication): Fine-Tuning of the Response • Signaling Efficiency: Scaffolding Proteins and Signaling Complexes – Scaffolding proteins are large relay proteins to which several other relay proteins are simultaneously attached to increase the efficiency of signal transduction. – In this figure, the scaffolding protein simultaneously binds to a specific activated membrane receptor and three different protein kinases. This physical arrangement facilitates signal transduction by these molecules.

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BIOLOGY I. Chapter 11 – Cell Communication

Cell Signaling (Communication): Fine-Tuning of the Response • Termination of the Signal – If a signaling pathway component becomes locked into one state, whether active or inactive, dire consequences for the organism can result, therefore, the changes that signals produce are reversible. – Signal response is terminated quickly by the reversal of ligand binding. When signal molecules leave the receptor, the receptor reverts to its inactive form and relay molecules are inactivated.

– In this way, the cell is soon ready to respond to a new signal. Evelyn I. Milian - Instructor

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BIOLOGY I. Chapter 11 – Cell Communication

The Three Stages of Cell Signaling: An Analogy Cells

Analogy

The target cell’s detection of a signal molecule from outside the cell, when it binds to a receptor protein.

A TV camera (receptor) is shooting a scene.

Transduction The conversion of a signal from outside the cell to a form that can bring about a specific cellular response.

The picture is converted to electrical signals (transduction pathway) that are understood by the TV in your house.

Response

The electrical signals are converted to a picture on your TV screen (the response).

Reception

The change in a specific cellular activity brought about by a transduced signal from outside the cell. Evelyn I. Milian - Instructor

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BIOLOGY I. Chapter 11 – Cell Communication

Evelyn I. Milian - Instructor

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BIOLOGY I. Chapter 11 – Cell Communication

Evelyn I. Milian - Instructor

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BIOLOGY I. Chapter 11 – Cell Communication

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Brooker, Robert J.; Widmaier, Eric P.; Graham, Linda E.; Stiling, Peter D. (2008). Biology. The McGraw-Hill Companies, Inc. NY, USA.

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Campbell, Neil A.; Reece, Jane B., et al. (2011). Biology. Ninth Edition. Pearson Education, Inc.-Pearson Benjamin Cummings. CA, USA.

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Ireland, K.A. (2011). Visualizing Human Biology. Second Edition. John Wiley & Sons, Inc. NJ, USA.

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Mader, Sylvia S. (2010). Biology. Tenth Edition. The McGraw-Hill Companies, Inc. NY, USA.

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Martini, Frederic H.; Nath, Judi L. (2009). Fundamentals of Anatomy & Physiology. Eighth Edition. Pearson Education, Inc. – Pearson Benjamin Cummings. CA, USA.

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Solomon, Eldra; Berg, Linda; Martin, Diana W. (2008). Biology. Eighth Edition. Cengage Learning. OH, USA.

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Starr, Cecie. (2008). Biology: Concepts and Applications , Volume I. Thompson Brooks/Cole. OH, USA.

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Tortora, Gerard J.; Derrickson, Bryan. (2006). Principles of Anatomy and Physiology. Eleventh Edition. John Wiley & Sons, Inc. NJ, USA. www.wiley.com/college/apcentral. Evelyn I. Milian - Instructor

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