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Cell Communication Cell-to-cell communication is important for multicellular organisms Exchange of mating factors a factor Receptor a a Yeast cell, a factor mating type a Yeast cell, mating type a Mating a a New a/a cell a/a https://www.youtube.com/watch?v=TfpOKW dOolM (Start at 3:40 - ~ 6:00) https://www.youtube.com/watch?v=DY3SQA 79ZVo (only 1 second) chemical messengers cell junctions directly connect adjacent cells In local signaling, animal cells may communicate by direct contact Plasma membranes Gap junctions between animal cells Cell junctions Cell-cell recognition Plasmodesmata between plant cells Animals use local regulators (for short distance signals) ◦ EX: Humans: pass a note; text message; Celly; email; Facebook Plants and animals use chemicals called hormones (for long distance) Local signaling Long-distance signaling Target cell Secreting cell Local regulator diffuses through extracellular fluid Paracrine signaling Electrical signal along nerve cell triggers release of neurotransmitter Endocrine cell Neurotransmitter diffuses across synapse Secretory vesicle Target cell is stimulated Blood vessel Hormone travels in bloodstream to target cells Target cell Synaptic signaling Hormonal signaling http://www.bozemanscience.com/037-cellcommunication Earl Sutherland discovered how the hormone epinephrine acts on cells http://media.pearsoncmg.com/bc/bc_campbell_biology_7/mm2 /ch11/InstructorResources/medialib_tab_2/1.htm ◦Reception ◦Transduction ◦Response ◦ http://media.pearsoncmg.com/bc/bc_campbell_biology_7/ mm2/ch11/InstructorResources/medialib_tab_2/2.htm EXTRACELLULAR FLUID CYTOPLASM Plasma membrane Reception Receptor Signal molecule Transduction EXTRACELLULAR FLUID CYTOPLASM Plasma membrane Reception Transduction Receptor Relay molecules in a signal transduction pathway Signal molecule EXTRACELLULAR FLUID CYTOPLASM Plasma membrane Reception Transduction Response Receptor Activation of cellular response Relay molecules in a signal transduction pathway Signal molecule The binding between a signal molecule (ligand) and receptor is specific A conformational (shape) change in a receptor starts the process Most signal receptors are plasma membrane proteins Small or hydrophobic chemical messengers can readily cross the membrane and activate receptors ◦ Examples of hydrophobic messengers are the steroid and thyroid hormones of animals An activated hormone-receptor complex can act as a transcription factor, turning on specific genes Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein Hormonereceptor complex The steroid hormone testosterone passes through the plasma membrane. Testosterone binds to a receptor protein in the cytoplasm, activating it. The hormonereceptor complex enters the nucleus and binds to specific genes. DNA The bound protein stimulates the transcription of the gene into mRNA. mRNA NUCLEUS New protein The mRNA is translated into a specific protein. CYTOPLASM https://www.youtube.com/watch?v=qOVkedx DqQo (bozeman signal transduction) Most water-soluble signal molecules bind to specific sites on receptor proteins in the plasma membrane There are three main types of membrane receptors: 1. G-protein-linked receptors 2. Receptor tyrosine kinases 3. Ion channel receptors A G-protein-linked receptor is a plasma membrane receptor that works with the help of a G protein The G-protein acts as an on/off switch: If GDP is bound to the G protein, the G protein is inactive Signal-binding site Segment that interacts with G proteins G-protein-linked receptor Receptor tyrosine kinases are membrane receptors that attach phosphates to tyrosines A receptor tyrosine kinase can trigger multiple signal transduction pathways at once Signal molecule Signal-binding site a Helix in the membrane Signal molecule Tyrosines Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Receptor tyrosine kinase proteins (inactive monomers) CYTOPLASM Dimer Activated relay proteins Tyr Tyr Tyr Tyr Tyr Tyr 6 ATP Activated tyrosinekinase regions (unphosphorylated dimer) 6 ADP P Tyr P Tyr P Tyr Tyr P P Tyr P Tyr Fully activated receptor tyrosine-kinase (phosphorylated dimer) P Tyr P Tyr P Tyr P Tyr P Tyr P Tyr Inactive relay proteins Cellular response 1 Cellular response 2 An ion channel receptor acts as a gate when the receptor changes shape When a signal molecule binds as a ligand to the receptor, the gate allows specific ions, such as Na+ or Ca2+, through a channel in the receptor Signal molecule (ligand) Gate closed Ligand-gated ion channel receptor Ions Plasma membrane Gate open Cellular response Gate closed https://www.youtube.com/watch?v=_GraY9A 8N4Q Transduction usually involves multiple steps Multistep pathways can amplify a signal: A few molecules can produce a large cellular response The molecules that relay a signal from receptor are mostly proteins Like falling dominoes, the receptor activates another protein, which activates another, and so on, until the protein producing the response is activated In many pathways, the signal is transmitted by a cascade of protein phosphorylations Turning activities on and off Signal molecule Receptor Activated relay molecule Inactive protein kinase 1 Active protein kinase 1 Inactive protein kinase 2 ATP ADP Pi P Active protein kinase 2 PP Inactive protein kinase 3 ATP ADP Pi Active protein kinase 3 PP Inactive protein P ATP P ADP Pi PP Active protein Cellular response Second messengers are small, nonprotein, water-soluble molecules or ions ◦ The extracellular signal molecule that binds to the membrane is a pathway’s “first messenger” ◦ Second messengers can spread through cells by diffusion ◦ Second messengers are important in G-protein-linked receptors and tyrosine kinases • • Cyclic AMP (cAMP) is one of the most widely used second messengers Adenylyl cyclase, an enzyme in the plasma membrane, converts ATP to cAMP in response to an extracellular signal Phosphodiesterase Adenylyl cyclase Pyrophosphate P ATP H2O Pi Cyclic AMP AMP Many signal molecules trigger formation of cAMP First messenger (signal molecule such as epinephrine) Adenylyl cyclase G protein G-protein-linked receptor GTP ATP cAMP Second messenger Protein kinase A Cellular responses Calcium ions (Ca2+) act as a second messenger in many pathways Calcium is an important second messenger because cells can regulate its concentration EXTRACELLULAR FLUID Plasma membrane Ca2+ pump ATP Mitochondrion Nucleus CYTOSOL Ca2+ pump Endoplasmic reticulum (ER) ATP Key Ca2+ pump High [Ca2+] Low [Ca2+] EXTRACELLULAR Signal molecule FLUID (first messenger) G protein DAG GTP G-protein-linked receptor IP3-gated calcium channel Endoplasmic Ca2+ reticulum (ER) CYTOSOL Phospholipase C PIP2 IP3 (second messenger) EXTRACELLULAR Signal molecule FLUID (first messenger) G protein DAG GTP G-protein-linked receptor Phospholipase C IP3 (second messenger) IP3-gated calcium channel Endoplasmic Ca2+ reticulum (ER) CYTOSOL PIP2 Ca2+ (second messenger) EXTRACELLULAR Signal molecule FLUID (first messenger) G protein DAG GTP G-protein-linked receptor Phospholipase C PIP2 IP3 (second messenger) IP3-gated calcium channel Endoplasmic Ca2+ reticulum (ER) CYTOSOL Ca2+ (second messenger) Various proteins activated Cellular responses Reception Binding of epinephrine to G-protein-linked receptor (1 molecule) Transduction Inactive G protein Active G protein (102 molecules) Inactive adenylyl cyclase Active adenylyl cyclase (102) ATP Cyclic AMP (104) Inactive protein kinase A Active protein kinase A (104) Inactive phosphorylase kinase Active phosphorylase kinase (105) Inactive glycogen phosphorylase Active glycogen phosphorylase (106) Response Glycogen Glucose-1-phosphate (108 molecules) GENE REGULATION: Many other signaling pathways regulate the synthesis of enzymes or other proteins, usually by turning genes on or off in the nucleus The final activated molecule may function as a transcription factor Growth factor Reception Receptor Phosphorylation cascade Transduction CYTOPLASM Inactive transcription Active transcription factor factor P Response DNA Gene NUCLEUS mRNA Signal molecule Receptor Relay molecules Response 1 Cell A. Pathway leads to a single response Response 2 Response 3 Cell B. Pathway branches, leading to two responses Activation or inhibition Response 4 Cell C. Cross-talk occurs between two pathways Response 5 Cell D. Different receptor leads to a different response LE 11-16 Signal molecule Plasma membrane Receptor Three different protein kinases Scaffolding protein LE 11-16 Signal molecule Plasma membrane Receptor Three different protein kinases Scaffolding protein Inactivation mechanisms are an essential aspect of cell signaling When signal molecules leave the receptor, the receptor reverts to its inactive state https://www.youtube.com/watch?v=DusAds_-lU