Cell Communication 3d1: Cell communication processes share common features that reflect a shared evolutionary history 3d2: Cells communicate with each other through direct contract with other cells or from a distance via chemical signaling 3d3: Signal transduction pathways link signal reception with cellular response 3d4: Changes in signal transduction pathways can alter cellular response

DSJ – Pair Share What is communication? What purpose does it serve? What are the different ways humans commuicate? Do other organisms (bacteria, plants, animals) communicate? Predict two ways cells might communicate with one another.

Overview Cell in a multicellular organism must communicate to coordinate activities  lack of communication results in chaos Traffic signals  image what traffic would be like without them In studying how cells signal and interpret signals they receive, biologists have discovered some universal mechanisms of communication; same small set of cell- signaling mechanisms show up again and again in many lines of biological research (bacteria, animals, plants, yeast)

Example of primitive cells communicating Receptor  factor a factor a  Exchange of mating factors Yeast cell, mating type a mating type  Mating New a/ cell a/ 1 2 3 Example of primitive cells communicating Communications between mating yeast: Use chemical signals to identify opposite mating types Cells of mating type a secrete a signal molecule called a factor, which can bind to receptors on nearby ∂ type cells

Second Example of primitive cell communication Individual rod- shaped cells Spore-forming structure (fruiting body) Aggregation in process Fruiting bodies 0.5 mm 1 3 2 Communication among bacteria: Use chemicals to share information about nutrient availability When food is scarce, starving cells secrete a molecule that reaches neighboring cells and stimulates them to aggregate  forming a fruiting body that produces thick-walled spores capable of surviving until the environment improves In single-celled organisms signal transduction pathways influence how the cell responds to its environment: Quorum sensing: bacteria’s ability to sense the local population size based on the concentration of signaling molecules Can lead to coordination of activities Biofilms: collections of bacteria that often form recognizable structures that contain regions of specialized functions.

Three many ways cells communicate Direct contact (post-it note – direct – messages is hand transferred) Immune cells using antigen presenting cells Plasmodesmata/Gap junctions Short Distance (email – sent to a specific individual) Local Regulators such as neurotransmitters Long distances (Facebook – broadcasted to multiple cells) Endocrine cells release hormones (chemicals) through blood to communicate with target cells (cell meant to receive the message)

Plasma membranes Gap junctions between animal cells (a) Cell junctions Plasmodesmata between plant cells (b) Cell-cell recognition Direct Contact Cell junctions: allow molecules to pass between adjacent (touching) cells without crossing the plasma membrane Gap junctions: term used to refer to the junctions in animal cells Plasmodesmata: term used to refer to the junction in plant cells Cell-to-cell recognition: cells in animal cells may communicate by interaction between molecules protruding from their surfaces

Short Distance (Local Signaling) Paracrine signaling: Secreting cell acts on multiple nearby cells by excreting local regulators Synaptic signaling: cell releases neurotransmitters molecules into a synapse, stimulating ONE target cell Local regulators: message molecules that travel short distances Local signaling Target cell Secretory vesicle Secreting cell Local regulator diffuses through extracellular fluid (a) Paracrine signaling (b) Synaptic signaling is stimulated Neurotransmitter diffuses across synapse Electrical signal along nerve cell triggers release of neurotransmitter

Long Distance Signaling Endocrine cell Blood vessel Hormone travels in bloodstream to target cells Target cell (c) Hormonal signaling Electrical signals along a nerve cell Hormones: chemicals released in the blood stream to target cells; secreted by endocrine glands/organs (pancreas, hypothalmus…)

Signal Transduction Pathways A series of steps by which signal on a cell’s surface is converted into a specific cellular response Three processes: Reception Transduction Response EXTRACELLULAR FLUID Plasma membrane CYTOPLASM Receptor Signaling molecule Relay molecules in a signal transduction pathway Activation of cellular response Transduction Response 2 3 Reception 1

Signal Transduction Pathway: Reception Reception: target cell detects the signaling molecule; detection takes place when the signaling molecules binds to the receptor protein located at the cell’s surface or inside the cell Ligand: general name used to refer to the substance that binds to a receptor A shape change in the receptor is often the initial transductions of the signal Reception 1 EXTRACELLULAR FLUID Signaling molecule Plasma membrane CYTOPLASM Receptor

Three main types of membrane receptors G protein-coupled receptors: receptor that workswith the help of a G protein Receptor tyrosine kinases: attach phosphates to tyrosines; can trigger multiple signal transduciton pathways at once Ion channel receptors: acts as a gate when receptor changes shape; gate allows specific ions, such as Na+ or Ca2+, through a channel in the receptor

G protein-coupled receptor When GDP is bound to the G protein, the G protein is inactive When signaling molecule binds to receptor, receptor is activated and changes shape, shape change cause receptor to bind with G protein, causing GTP to displace GDP Activated G protien travels from the receptor and binds with an enzyme, altering the enzymes shape and turning it on; the enzyme leads to a cellular response G protein also acts as a GTPase enzyme (breaks down GTP to GDP. G protein becomes inactive again and is available to be reused G protein-coupled receptor Plasma membrane Enzyme G protein (inactive) GDP CYTOPLASM Activated enzyme GTP Cellular response P i Signaling molecule Inactive 1 2 3 4

Receptor Tyrosine Kinases Before the signaling molecules binds, the receptors exist as individuals polypeptides Binding causes two receptor polypeptides to associate closely with each other, form a dimer (dimerization) Dimerization activates the tyrosine kinase region of each polypeptide; each tyrosine kinase adds a phosphate from an ATP Receptor protein is fully activated, recognized by relay proteins; each protein binds to a phosphorylated tyrosine, changes structure; each activated protein triggers a transduction pathway, leading to cellular response Signaling molecule (ligand) Ligand-binding site  Helix Tyrosines Tyr Receptor tyrosine kinase proteins CYTOPLASM molecule Dimer Activated relay proteins P Cellular response 1 response 2 Inactive relay proteins Activated tyrosine kinase regions Fully activated receptor tyrosine kinase 6 6 ADP ATP 1 2 3 4

Ion channel receptors Signaling molecule (ligand) Gate closed Ions Ligand-gated ion channel receptor Plasma membrane Gate open Cellular response Gate closed 3 2 1 Ligand-gated ion channel receptor in which the gate remains closed until a ligand binds to the receptor When the ligand binds to the receptor and the gate opens, specific ions can flow through the channel and rapidly change the concentration of that particular ion inside the cell. This change may directly affect the activity of the cell in some way. When the ligand dissociates form this receptor, the gate closes and ions no longer enter the cell

Intracellular Receptors Hormone (testosterone) EXTRACELLULAR FLUID Receptor protein Plasma membrane Hormone- receptor complex DNA mRNA NUCLEUS New protein CYTOPLASM Intracellular Receptors Some receptor proteins are intracellular, found in the cytoplasm or nucleus of target cells Small or hydrophobic chemical messengers can cross the membrane and activate receptors; examples = hormones Can act as a transcription factor (proteins that are needed to turn on genes)

Signal Transduction Pathway: Transduction Signal transductions usually involves multiple steps; allows for amplification of the signal, and opportunities for coordination and regulation Like falling dominoes, the receptor activates another protein, which activates another, and so on, until the protein producing the response is activated At each step, the signal is transduced into a different form, usually a shape change in a protein A receptor protein recognizes a signal molecule, causing the receptor protein to change shape which initiates transduction of the signal which ultimately leads to a response from the cell (movement of the cell, expression of a gene (transcription of DNA into mRNA). Can be thought of as a cascade

Protein Phosphorylation and Dephosphorylation Signaling molecule Receptor Activated relay molecule Inactive protein kinase 1 Active protein kinase 2 ATP ADP P PP 3 i Cellular response Phosphorylation cascade Many signal transduction pathways occur as a result of a cascade of protein phosphorylation. Protein kinases: enzyme that transfers phosphates from ATP to protein This process is called phosphorylation Protein phosphatases: enzyme that removes the phosphates from proteins This process is called dephosphorylation This phosphorylation and dephosphorylation system acts as a molecular switch, turning activities on and off

It’s not all about proteins Most of the molecules involved in Signal Transduction are proteins; however, there are small molecules that act as relay messengers and are often essential to the cascade, these molecules are called second messengers Two common second messengers are cyclic AMP (cAMP) and calcium ions

Cyclic AMP cyclic adenosine monophosphate; cyclic AMP; cAMP First messenger G protein Adenylyl cyclase GTP ATP cAMP Second messenger Protein kinase A G protein-coupled receptor Cellular responses cyclic adenosine monophosphate; cyclic AMP; cAMP An enzyme embedded in the plasma membrane (adenylyl cyclase – you do not need to memorize the name of the enzyme) converts ATP to cAMP in response to an extracellular signal (such as epinephrine binding to a protein receptor) When epinephrine outside the cell binds to a specific receptor protein, the protein activates adenylyl cyclase, which in turn can catalyze the synthesis of many molecules of cAMP  because enzyme is reusable cAMP can be boosted 20-fold in seconds cAMP usually activates protein kinase A, which phosphorylates various other proteins  leading to a cellular response

Calcium Ions and Inositol Triphosphate (IP3) Calcium ions (Ca2+) act as a second messenger in many pathways Calcium is an important second messenger because cells can regulate its concentration Pathways leading to the release of calcium involve inositol triphosphate (IP3) as additional second messengers Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

EXTRA- CELLULAR FLUID Signaling molecule (first messenger) G protein Fig. 11-13-3 EXTRA- CELLULAR FLUID Signaling molecule (first messenger) G protein DAG GTP G protein-coupled receptor PIP2 Phospholipase C IP3 (second messenger) IP3-gated calcium channel Figure 11.13 Calcium and IP3 in signaling pathways Endoplasmic reticulum (ER) Various proteins activated Cellular responses Ca2+ Ca2+ (second messenger) CYTOSOL

Nuclear and Cytoplasmic Responses Ultimately, a signal transduction pathway leads to regulation of one or more cellular activities The response may occur in the cytoplasm or may involve action in the nucleus Many 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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Growth factor Reception Receptor Phosphorylation cascade Transduction Fig. 11-14 Growth factor Reception Receptor Phosphorylation cascade Transduction CYTOPLASM Inactive transcription factor Active transcription factor Figure 11.14 Nuclear responses to a signal: the activation of a specific gene by a growth factor Response P DNA Gene NUCLEUS mRNA

Fine-Tuning of the Response Multistep pathways have two important benefits: Amplifying the signal (and thus the response) Contributing to the specificity of the response Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Signal Amplification Enzyme cascades amplify the cell’s response At each step, the number of activated products is much greater than in the preceding step Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Termination of the Signal Inactivation mechanisms are an essential aspect of cell signaling When signal molecules leave the receptor, the receptor reverts to its inactive state Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings