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Cell Communication
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Cell Communication Cell-to-cell communication is absolutely essential for multicellular organisms and is also important for many unicellular organisms Cells must communicate to coordinate their activities
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The “Cellular Internet”
Biologists have discovered some universal mechanisms of cellular regulation, involving the same small set of cell-signaling mechanisms External signals are converted into responses within the cell
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Evolution of Cell Signaling
Yeast cells Identify their mates by cell signaling factor Receptor Exchange of mating factors. Each cell type secretes a mating factor that binds to receptors on the other cell type. 1 Mating. Binding of the factors to receptors induces changes in the cells that lead to their fusion. New a/ cell. The nucleus of the fused cell includes all the genes from the a and cells. 2 3 Yeast cell, mating type a mating type a/ a
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Methods used by Cells to Communicate
Cell-Cell communication Cell Signaling using chemical messengers Plasma membranes Plasmodesmata between plant cells Gap junctions between animal cells Local regulator diffuses through extracellular fluid Target cell Secretory vesicle Electrical signal along nerve cell triggers release of neurotransmitter Neurotransmitter diffuses across synapse is stimulated Local signaling
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Local signaling over short distances
Cell-Cell Recognition Local regulators Paracrine (growth factors) Synaptic (neurotransmitters) 2. Long distance signaling Hormones
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Cell-Cell Communication
Animal and plant cells Have cell junctions that directly connect the cytoplasm of adjacent cells Plasma membranes Plasmodesmata between plant cells Gap junctions between animal cells Figure 11.3 (a) Cell junctions. Both animals and plants have cell junctions that allow molecules to pass readily between adjacent cells without crossing plasma membranes.
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Cell-Cell Communication
Animal cells use gap junctions to send signals cells must be in direct contact protein channels connecting two adjoining cells Gap junctions between animal cells
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Cell-Cell Communication
Plant cells use plasmodesmata to send signals cells must be in direct contact gaps in the cell wall connecting the two adjoining cells together Plasmodesmata between plant cells
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Local Signaling: Cell-Cell Recognition
In local signaling, animal cells may communicate via direct contact Membrane bound cell surface molecules Glycoproteins Glyolipids (Cell-cell recognition. Two cells in an animal may communicate by interaction between molecules protruding from their surfaces.
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Local Signaling: Local Regulators
In other cases, animal cells Communicate using local regulators Only work over a short distance (a) Paracrine signaling. A secreting cell acts on nearby target cells by discharging molecules of a local regulator (a growth factor, for example) into the extracellular fluid. (b) Synaptic signaling. A nerve cell releases neurotransmitter molecules into a synapse, stimulating the target cell. Local regulator diffuses through extracellular fluid Target cell Secretory vesicle Electrical signal along nerve cell triggers release of neurotransmitter Neurotransmitter diffuses across synapse is stimulated Local signaling
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Long-distance Signaling: Hormones
In long-distance signaling Both plants and animals use hormones Hormone travels in bloodstream to target cells (c) Hormonal signaling. Specialized endocrine cells secrete hormones into body fluids, often the blood Hormones may reach virtually all body cells. Long-distance signaling Blood vessel Target cell Endocrine cell
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Long-Distance Signaling
Nervous System in Animals Electrical signals through neurons Endocrine System in Animals Uses hormones to transmit messages over long distances Plants also use hormones Some transported through vascular system Others are released into the air
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How do Cells Communicate?
Earl W. Sutherland Discovered how the hormone epinephrine acts on cells
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How do Cells Communicate?
Sutherland suggested that cells receiving signals went through three processes Reception Transduction Response Called Signal transduction pathways Convert signals on a cell’s surface into cellular responses Are similar in microbes and mammals, suggesting an early origin
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How do Cells Communicate?
The process must involve three stages Reception - a chemical signal binds to a cellular protein, typically at the cell’s surface
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2. Transduction - binding leads to a change in the receptor that triggers a series of changes along a signal-transduction pathway
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3. Response - the transduced signal triggers a specific cellular response
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Signal Transduction Animation
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Signal molecules and Receptor Proteins
A cell targeted by a particular chemical signal has a receptor protein that recognizes the signal molecule recognition occurs when the signal binds to a specific site on the receptor because it is complementary in shape
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When ligands (small molecules that bind specifically to a larger molecule) attach to the receptor protein, the receptor typically undergoes a change in shape this may activate the receptor so that it can interact with other molecules
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Signal Molecules most signal molecules are water-soluble and too large to pass through the plasma membrane they influence cell activities by binding to receptor proteins on the plasma membrane binding leads to change in the shape of the receptor these trigger changes in the intracellular environment
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There are three common types of membrane receptor proteins:
G-protein coupled receptors Receptor tyrosine-kinases Ion channel receptors
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1. Reception A signal molecule, a ligand, binds to a receptor protein in a lock and key fashion, causing the receptor to change shape. Most receptor proteins are in the cell membrane but some are inside the cell.
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G Protein- Coupled Receptor
the receptor consists of seven alpha helices spanning the membrane
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G-Protein Receptors Inactive enzyme Plasma membrane G protein-coupled
Activated receptor Signaling molecule Enzyme GDP 1 2 GDP GTP CYTOPLASM G protein (inactive) Activated enzyme i GTP GDP P 3 4 Cellular response
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effective signal molecules include yeast mating factors, epinephrine, other hormones, and neurotransmitters Several human diseases are the results of activities, including bacterial infections, that interfere with G protein function botulism cholera pertussis
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Receptor tyrosine kinases
Signal molecule Signal-binding site CYTOPLASM Tyrosines Signal molecule Helix in the Membrane Tyr Dimer Receptor tyrosine kinase proteins (inactive monomers) P Cellular response 1 Inactive relay proteins Activated relay proteins Cellular response 2 Activated tyrosine- kinase regions (unphosphorylated dimer) Fully activated receptor tyrosine-kinase (phosphorylated 6 ATP ADP
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Ligand-gated Ion Channels
Ligand-gated ion channels are protein pores that open or close in response to a chemical signal this allows or blocks ion flow, such as Na+ or Ca2+ binding by a ligand to the extracellular side changes the protein’s shape and opens the channel ion flow changes the concentration inside the cell
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Ion Channel Receptors Very important in the nervous system
Gate closed 1 Ions Signaling molecule (ligand) Very important in the nervous system Signal triggers the opening of an ion channel Depolarization Triggered by neurotransmitters Ligand-gated ion channel receptor Plasma membrane 2 Gate open Cellular response 3 Gate closed
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2. Transduction Transduction: Cascades of molecular interactions relay signals from receptors to target molecules in the cell Multistep pathways Can amplify a signal (Amplifies the signal by activating multiple copies of the next component in the pathway) Provide more opportunities for coordination and regulation At each step in a pathway, the signal is transduced into a different form, commonly a conformational change in a protein.
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Transduction: A Phosphorylation Cascade Signaling molecule Receptor
Activated relay molecule Inactive protein kinase 1 Active protein kinase 1 Inactive protein kinase 2 ATP Phosphorylation cascade ADP Active protein kinase 2 P PP P i Inactive protein kinase 3 ATP ADP Active protein kinase 3 P PP P i Inactive protein ATP ADP P Active protein Cellular response PP P i
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Protein Phosphorylation and Dephosphorylation
Many signal pathways Include phosphorylation cascades In this process, a series of protein kinases add a phosphate to the next one in line, activating it Phosphatase enzymes then remove the phosphates
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A phosphorylation cascade
Signal molecule Active protein kinase 1 2 3 Inactive protein kinase Cellular response Receptor P ATP ADP PP Activated relay molecule i Phosphorylation cascade P A relay molecule activates protein kinase 1. 1 2 Active protein kinase 1 transfers a phosphate from ATP to an inactive molecule of protein kinase 2, thus activating this second kinase. Active protein kinase 2 then catalyzes the phos- phorylation (and activation) of protein kinase 3. 3 Enzymes called protein phosphatases (PP) catalyze the removal of the phosphate groups from the proteins, making them inactive and available for reuse. 5 Finally, active protein kinase 3 phosphorylates a protein (pink) that brings about the cell’s response to the signal. 4
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About 1% of our genes are thought to code for kinases.
The transduction stage of signaling is often a multistep process that amplifies the signal. About 1% of our genes are thought to code for kinases.
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Small Molecules and Ions as Second Messengers
Secondary messengers Are small, nonprotein, water-soluble molecules or ions
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Cyclic AMP Many G-proteins trigger the formation of cAMP, which then acts as a second messenger in cellular pathways. ATP GTP cAMP Protein kinase A Cellular responses G-protein-linked receptor Adenylyl cyclase G protein First messenger (signal molecule such as epinephrine)
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Cyclic AMP Cyclic AMP (cAMP) Is made from ATP O –O N O P OH CH2 NH2
H2O HO Adenylyl cyclase Phoshodiesterase Pyrophosphate Cyclic AMP AMP i
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3. Response Many possible outcomes
Growth factor Receptor Reception Many possible outcomes This example shows a transcription response Phosphorylation cascade Transduction CYTOPLASM Inactive transcription factor Active transcription factor Response P DNA Gene NUCLEUS mRNA
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Specificity of the signal
The same signal molecule can trigger different responses Many responses can come from one signal! Signaling molecule Receptor Relay molecules Response 1 Response 2 Response 3 Cell A. Pathway leads to a single response. Cell B. Pathway branches, leading to two responses.
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The signal can also trigger an activator or inhibitor
The signal can also trigger multiple receptors and different responses Activation or inhibition Response 4 Response 5 Cell C. Cross-talk occurs between two pathways. Cell D. Different receptor leads to a different response.
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Response- cell signaling leads to regulation of transcription (turn genes on or off) or cytoplasmic activities.
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Long-distance Signaling - Intracellular signaling includes hormones that are hydrophobic and can cross the cell membrane. Once inside the cell, the hormone attaches to a protein that takes it into the nucleus where transcription can be stimulated. Testosterone acts as a transcription factor.
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Bind to intracellular receptors
Steroid hormones Bind to intracellular receptors Hormone (testosterone) EXTRACELLULAR FLUID Receptor protein DNA mRNA NUCLEUS CYTOPLASM Plasma membrane Hormone- receptor complex New protein 1 The steroid hormone testosterone passes through the plasma membrane. Testosterone binds to a receptor protein in the cytoplasm, activating it. 2 The hormone- receptor complex enters the nucleus and binds to specific genes. 3 The bound protein stimulates the transcription of the gene into mRNA. 4 The mRNA is translated into a specific protein. 5
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Signaling Efficiency: Scaffolding Proteins and Signaling Complexes
Can increase the signal transduction efficiency Signal molecule Receptor Scaffolding protein Three different protein kinases Plasma membrane
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Termination of the Signal
Signal response is terminated quickly By the reversal of ligand binding
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