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Cell Communication Types of Cell Communication • Cells in multicellular organisms communicate via chemical messages • Local (cells are adjacent) • Long-distance • Specific target cells recognize and respond to a specific signaling molecule Local Cell Communication • Cells that are adjacent may communicate via • Cell Junctions – molecules pass via the cytoplasm using cell junctions between cells (plant and animal cells) • Cell-cell recognition – Communication by interaction of molecules protruding from the surface of the cells (Animal) Local Cell Communication • Cells that are near each other, but not necessarily adjacent may also communicate via • Paracrine Signaling – A secreting cell acts on nearby target cells by discharging ‘messenger’ molecules of a local regulator into the extracellular fluid (for example: growth factor) • Synaptic Signaling – A nerve cell releases neurotransmitter molecules into a synapse, stimulating the target cell Long-Distant Cell Communication • At times a signal cell and target cell are farther apart • Hormonal/Endocrine Signaling – Specialized cells release hormone molecules that travel via the circulatory system to the target cells • Plants use similar system using vessels or diffusion as travel • The nervous system can also be considered a part of longdistance communication Stages of Cell Signaling • Reception • Transduction • Response Reception • A receptor protein on or near the target cell allows the cell to detect and react to messages • The signaling molecule is complimentary in shape and site specific on the receptor molecule • Ligand (molecule that specifically binds to another) binding generally causes a receptor protein to change shape and may cause activation of the receptor • Causes the combining of 2 or more receptor molecules, leading to other molecular events Types of Receptors • Plasma Membrane Receptors • Most are water-soluble and embedded in the cell membrane • Transmits info from extracellular environs to inside the cell via shape change or aggregation • Examples: G protein-coupled receptors, receptor tyrosine kinases, ion channel receptors G Protein-Coupled Receptors • Composed of seven α helices that span the plasma membrane with loops that act as binding sites • Binds energy-rich GTP • Functions include: role in embryonic development, sensory reception (vision and smell) • Involved in many bacterial diseases (Ex: Cholera) • Toxins produced by these diseases interfere with the G protein • Many medicines also interact with G protein pathways G ProteinCoupled Receptors • G protein functions as an ‘on/off’ switch for the molecule depending on whether GDP (inactive) or GTP (active) is attached • Signaling molecule causes a shape change. The cytoplasmic side binds to the G protein, causing a GDP to be displaced by a GTP, activating the molecule. • Activated G protein then binds to an enzyme, triggering the next step in a pathway. • GTP is hydrolyzed, creating GDP and leaving the G protein inactive Receptor Tyrosine Kinases • Receptors begin as individual polypeptides with ligand binding sites • The binding of a signaling molecule causes the polypeptides to associate creating a dimer and activating the tyrosine kinase region • Each tyrosine kinase adds a P from ATP, fully activating the receptor protein • Specific relay proteins will now bind to specific phosphorylated tyrosine, causing a structural change activating the bound proteins and triggering a transduction pathway Ion Channel Receptors • Gate on an ion channel remains closed until a ligand binds to the receptor • Specific ions can flow through when gate opens, rapidly changing the concentration of those ions inside the cell • Ligand dissociates from the receptor closing the gate Types of Receptors • Intracellular Receptors • Found in either the cytoplasm or nucleus of target cells • A chemical messenger will need to pass through the plasma membrane • Tend to be either hydrophobic or small enough to cross • Examples: Steroid Hormones, Thyroid Hormones, nitric oxide Steroid Hormone • Testosterone passes through the cell membrane, binds with the receptor molecule becoming active. • The active form then enters the nucleus and turns on specific genes that control male sex characteristics • Transcription factors – control which genes are turned on (transcribed into mRNA) Transduction • Binding of the signaling molecule changes the receptor protein and initiates transduction • May involve a single step, but more often is a sequence of steps in a pathway • For plasma membrane receptors this is usually a multistep pathway • May include activation of proteins by addition or removal of phosphate groups or release of ions or small molecules • Multiple steps allows for amplification, greater coordination and regulation of the signal Signal Transduction Pathways • The binding of a signaling molecule begins the pathway with each step leading to another step and eventually leading to a cellular response • Protein kinase is a relay molecule and is used to pass a P molecule from ATP to a protein • Several protein kinases may act on each other in a chain or phosphorylation cascade • Enzymes called protein phosphatases rapidly remove P groups from proteins, inactivating proteins and turning off the pathway Ions and Molecules as 2nd Messengers • Signal transduction pathways will sometimes involve nonprotein molecules that are water-soluble or ions called 2nd messengers • Can readily spread throughout the cell via diffusion • Examples: Cyclic AMP, Calcium ions and IP3 Cyclic AMP • Cyclic adenosine monophosphate (cAMP) • An enzyme (adenylyl cyclase) in the plasma membrane converts ATP to cAMP in response to a signal (first messenger) • cAMP broadcasts the signal to the cytoplasm, usually activating protein kinase A which phosphorylates other proteins Example: Epinephrine Calcium Ions and IP3 • More commonly used than cAMP • Signal induces an increase in cytosolic concentration of Ca2+ • Concentration usually much higher outside of cell and within certain organelles (ER, mitochondria, chloroplasts) • Rise in CA2+ usually accomplished by release of calcium from ER • Causes muscle cell contraction, cell division, secretion of substances • Used by neurotransmitters, growth factors and some hormones • Inositol triphosphate (IP3) and diacylglycerol (DAG) are other 2nd messengers Response • The final outcome of the message which is the regulation of some cellular activity • Response may occur in cytoplasm or nucleus, but many regulate protein synthesis by turning specific genes on and off Fine-Tuning the Response • Signal Amplification • Specificity of Cell Signaling and Coordination of the Response • Pathway leads to a single response • Pathway branches leading to two responses • Cross-talk occurs between 2 pathways • Different receptor leads to a different response • Signaling Efficiency • May be related to the presence of scaffolding proteins that hold several relay proteins which may help to hold pathways together • Termination of Signal Apoptosis • Programmed cell suicide • Occurs when cells are infected, damaged or old/beyond cell usefulness • Signals for death may come from outside the cell or via alarms inside • Alarms come from either the nucleus (DNA has suffered irreparable damage) or the ER (excessive protein misfolds) • DNA is chopped up, organelles are fragmented, and the cell shrinks and goes through blebbing (becomes lobed) • The cells parts are then packaged up into vesicles and are digested by scavenger cells