Bio101lec03 Ch11-12 Cell Signaling and Cycle (.Pdf)
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Chapter 11: Cell Communication. Why do cells need to signal? • Cells communicate with each other through cell-cell signaling. • Signaling molecules are the chemical messengers used (sometimes called ligands) Signal transduction pathways •Are similar in microbes and mammals, suggesting an early origin –Suggests an evolutionary connection. 1 Exchange of ! factor mating factors. Receptor Each cell type secretes a mating factor a ! that binds to receptors on the other cell type. Yeast cell, a factor Yeast cell, mating type a mating type ! 2 Mating. Binding of the factors to receptors induces changes a ! in the cells that lead to their fusion. 3 New a/! cell. The nucleus of the fused cell a/ includes all the ! genes from the Figure 11.2 a and a cells. Signaling in multicellular organisms Long Distance Signaling • Can be both Local or Long-Distance •Endocrine: Signal is released into a carrier system, such as blood, which carries the molecules to the target cells, which can be far away. • Local Signaling – Examples of this are hormones. – Paracrine: The signaling molecule is released and diffuses Long-distance signaling to the neighboring cells. This is local Signaling. Endocrine cell Blood – Synaptic Signaling. Nerve cells signal across a synapse. vessel Local signaling Target cell Electrical signal along nerve cell triggers release of neurotransmitter Hormone travels in bloodstream to target cells Neurotransmitter Secretory diffuses across vesicle synapse Target cell Local regulator diffuses through Target cell (c) Hormonal signaling. Specialized extracellular fluid is stimulated endocrine cells secrete hormones (a) Paracrine signaling. A secreting cell acts (b) Synaptic signaling. A nerve cell into body fluids, often the blood. on nearby target cells by discharging releases neurotransmitter molecules Hormones may reach virtually all molecules of a local regulator (a growth into a synapse, stimulating the Figure 11.5 C body cells. factor, for example) into the extracellular target cell. Figure 11.5 A B fluid. • For most signals the signaling molecule does not The signal-transduction pathway enter the cell • The response of the cell to a signaling molecule is mediated – The signal is relayed through the membrane, from the through a signal-transduction pathway. outside to the inside. • This occurs through 3 steps. – Reception • How is this done? – Transduction – Response EXTRACELLULAR CYTOPLASM • The signaling molecule (ligand) binds to a FLUID Plasma membrane membrane receptor on the outside of the cell. 1 Reception 2 Transduction 3 Response • This receptor spans the membrane and has both Receptor an extracellular and a cytosolic domain. Activation of cellular response • The cytosolic domain changes shape when Relay molecules in a signal transduction pathway bound to ligand. – The ligand is not always a diffusible molecule Signal molecule Figure 11.6 Receptors G-Protein linked receptors • Are connected to a G-protein that is activated when a ligand binds to • There are three major types of membrane the receptor. • The activation triggers the displacement of the GDP by GTP. This receptors. activated G-protein then goes on to activate other proteins. • Example: Slime mold cAMP receptor system. – G-Protein linked receptors. Figure 11.7a – Tyrosine-Kinase Receptors – Ligand-gated Ion channels. Focus on the G-Protein linked receptors Know the other pathways! Tyrosine-Kinase Receptors. Ligand-gated Ion channels • Form dimers. Signal Gate closed Ions • Phosphorylate the tyrosine amino acids on the other receptor molecule • This activates the receptor dimer (ligand) • Binding of ligand opens up an ion channel. • Example: Growth factor receptor. Ligand-gated Plasma Signal Signal-binding sitea ion channel receptor Membrane molecule • The opening of the channel leads to a net flow of Signal !Helix in the molecule ions into or out of the cell. Membrane Gate open Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyrosines Tyr Tyr Tyr Tyr Tyr Tyr + 2+ Tyr Tyr Tyr Tyr • This triggers an intracellular response. Na , Ca Receptor tyrosine CYTOPLASM kinase proteins Dimer (inactive monomers) Cellular response Activated relay proteins Cellular P Tyr P Tyr Tyr P Tyr Tyr P Tyr response 1 Gate close Tyr Tyr PTyr Tyr P PTyr Tyr P Tyr P Tyr P Tyr Tyr P Cellular Tyr 6 ATP 6 ADP Tyr P response 2 Activated tyrosine- Fully activated receptor kinase regions tyrosine-kinase Inactive (unphosphorylated (phosphorylated relay proteins Figure 11.7 Figure 11.7 dimer) dimer) Intracellular Receptors. Transduction The signal is relayed via cascades of molecular interactions in the cell. • Small non polar molecules, Hormones, can travel through the membrane where they can bind to an internal receptor protein • Amplification of the signal can be achieved by phosphorylation cascades • Usually activates a transcription factor. and second messengers • Adding or removing phosphate groups regulates protein activity. Hormone EXTRACELLULAR • Kinases use ATP to phosphorylate molecules. (testosterone) FLUID 1 The steroid • Phosphatases remove phosphate groups from molecules. hormone testosterone passes through the plasma membrane. Signal molecule Plasma membrane Receptor 2 Testosterone binds protein to a receptor protein Receptor Activated relay Hormone- in the cytoplasm, molecule receptor activating it. Inactive complex protein kinase Active Phosphorylation 1 protein 3 The hormone- kinase receptor complex Inactive 1 enters the nucleus protein kinaseATP Active ADP P and binds to specific 2 protein PP kinase cascade DNA genes. Pi Inactive 2 mRNA 4 The bound protein protein kinaseATP Active ADP P stimulates the 3 protein transcription of PP kinase Pi 3 NUCLEUS New protein the gene into mRNA. Inactive ATP protein P 5 The mRNA is ADP Active Cellular translated into a PP protein response P i specific protein. Figure 11.6 CYTOPLASM Figure 11.9 Second messengers Nuclear response to a signal 2+ – cAMP and Ca or other small molecules (IP3, DAG) Regulate genes by activating transcription 1 A signal molecule binds 2 Phospholipase C cleaves a 3 DAG functions as factors that turn genes on or off to a receptor, leading to plasma membrane phospholipid a second messenger activation of phospholipase C. called PIP2 into DAG and IP3. in other pathways. EXTRA- Growth factor Reception Signal molecule CELLULAR Receptor (first messenger) FLUID G protein DAG GTP Phosphorylation cascade Figure 11.13 G-protein-linked PIP2 Transduction receptor Phospholipase C IP3 (second messenger) CYTOPLASM IP3-gated calcium channel Inactive Endoplasmic Various transcription Active Cellular factor transcription reticulum (ER) Ca2+ proteins response Response activated factor P Ca2+ DNA (second messenger) Gene 4 IP quickly diffuses through 5 Calcium ions flow out of 6 The calcium ions 3 mRNA the cytosol and binds to an IP3– the ER (down their con- activate the next NUCLEUS gated calcium channel in the ER centration gradient), raising protein in one or more Figure 11.14 membrane, causing it to open. the Ca2+ level in the cytosol. signaling pathways. The signaling is very specific Signal Transduction • Receptors only bind to a specific ligand. Signal molecule EXTRA- Signal molecule CELLULAR • The same signaling molecule can lead to (first messenger) FLUID different responses in different types of Receptor G protein cells. Relay DAG molecules GTP – Example: Epinephrine G-protein-linked PIP2 Phospholipase C receptor IP Response 1 Response Response 3 – In liver it triggers breakdown of glycogen (second messenger) 2 – In the heart it increase the heart beat. 3 IP3-gated calcium channel Endoplasmic Various Cellular reticulum (ER) Ca2+ proteins response activated Activation Ca2+ or inhibition (second messenger) Response 4 Response 5 Figure 11.17 Summary of signaling. Chapter 12 The Cell Cycle. Every living organism must be able to reproduce in • Via membrane proteins. order to survive. – G-Protein linked receptors. Many different G-proteins – Tyrosine-Kinase Receptors. • Reproduction occurs by Cell Division. – Ligand-gated Ion channels. – It is part of the Cell Cycle. – It results in genetically identical daughter cells • Directly Intracellular Receptors • The Cell Cycle is the foundation of life. – Non-polar molecules that bind to receptors inside cells. Usually activate transcription factors. • Unicellular organisms • Both can lead to amplification of signal. – Reproduce by cell division – Branching: Binding of signaling molecule can trigger several • Multicellular organisms depend on cell division for different responses inside cell. – Development from a fertilized cell – Combination of two different signals. – Growth – Repair Genome Brief review • The cells genetic information is called its genome. • Eukaryotic cell division consists of • The genome contains the recipe for running and building – Mitosis, the division of the nucleus the cell. – Cytokinesis, the division of the cytoplasm • The genome contains all the chromosomes. • The chromosome is made up of a very long linear DNA • In meiosis strand containing up to thousands of genes, each gene – Sex cells are produced after a reduction in specifying a specific protein. chromosome number • This strand is associated with various proteins that maintain the structure and control the activity of genes. • This DNA protein complex is called chromatin. – A cell can have 3 m long DNA strands even though it is only 10 !m long. The Cell Cycle is divided into Two Phases • DNA is Duplicated in S phase! Not in mitosis. • After the S phase each chromosome has an identical copy, the pair are Interphase