9 CHAPTER CELL COMMUNICATION AND REGULATION OF THE CELL CYCLE
Prepared by
Brenda Leady, University of Toledo
Copyright (c) The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
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A plasma membrane is essential for a cell It does isolate the cell from its surroundings A cell cannot survive if it cannot sense changes in the extracellular environment and respond to them
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Cell communication is the process of cells detecting and responding to signals in the extracellular environment Needed to coordinate cellular activities in a multicellular organism One important reason for cell communication is to promote cell division
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Cell communication or cell signaling involves incoming and outgoing signals Signals are agents that influence the properties of cells Signals affect the conformation of a receptor leading to a response in the cell
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Why do cells need to respond to signals?
1.
Need to respond to a changing environment
Adaptation or a cellular response is critical for survival Glucose acts as a signal to yeast cells to increase number of glucose transporters and enzymes allowing efficient uptake and use of glucose
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Why do cells need to respond to signals?
Cells need to communicate with each other
Cell-to-cell
communication Darwin and his son investigated phototropism Auxin is a signaling molecule transmitted from cell to cell and inhibited by the light
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Signals relayed between cells
1.
Direct intercellular signaling
Cell junctions allow signaling molecules to pass from one cell to another Some molecules are bound to the surface of cells and serve as signals to cell coming in contact with them Cells secrete signaling molecules that bind to their own cell surface or neighboring cells of the same type
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2.
Contact-dependent signaling
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Autocrine signaling
3.
Paracrine signaling
Signal does not affect cell secreting the signal but does influence cells in close proximity (synaptic signaling) Signals (hormones) travel long distances and are usually longer lasting
4.
Endocrine signaling
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3 stages of cell signaling
1. 2.
Receptor activation
Signaling molecule binds to receptor
Signal transduction
Activated receptor stimulates sequence of changes- signal transduction pathway
Several different responses
3.
Cellular response
Alter activity of 1 or more enzymes Alter structural protein function Change gene expression
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Ligand
Signaling molecule Binds noncovalently to receptor with high degree of specificity Binding and release between receptor and ligand relatively rapid Ligands alter receptor structureconformational change Hormone-receptor complex is an activated receptor that can initiate a cellular response
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Cell surface receptors
1.
Enzyme-linked receptors
Found in all living species Extracellular domain binds signal Causes intracellular domain to become functional catalyst Most are protein kinases
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2.
G-protein coupled receptors (GPCR)
Common in eukaryotes Protein contains 7 transmembrane segments Activated receptor binds to G protein Releases GDP and binds GTP instead GTP causes G protein to disassociate Subunit and b/g dimer interact with other proteins in a signaling pathway
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3. Ligand-gated ion channels
Plant and animal cells Ligand binding causes ion channels to open and ions to flow through the membrane Animals- signals between nerve and muscle cells, between 2 nerve cells, Ca2+ uptake
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Intracellular receptors
Most receptors on the plasma membrane but some are inside the cell Estrogen example
Passes
through membrane and binds to receptor in nucleus Dimer of estrogen-receptor complexes binds to DNA to activate transcription of specific genes
Transcription factors regulate transcription of specific genes
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Auxin example
Binding
of auxin in the cytosol activates TIR1 Gene regulation not direct Causes breakdown of inhibitory proteins With gene inhibition relieved, genes are transcribed
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Cellular response
Two-component regulatory system
Bacteria,
fungi and plants (not animals)
Sensor kinase
receptor Hydrolyzes ATP and phosphorylates Phosphate group transferred to response regulator
Enzyme-linked
Response regulator
Regulates
expression of many genes
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NarQ/ NarL
Two-component
regulatory system Senses presence of nitrate (NO3-) and nitrite (NO2-) Binding phosphorylates NarQ Transfers phosphate to NarL (response regulator) Activates genes involved in nitrate and nitrite metabolism and transport
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Second messengers
Signals binding to cell surface are first messenger Many signal transduction pathways lead to production of second messengers Examples
cAMP
Ca2+
Diacylglycerol
and inositol triphosphate
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Signal transduction cAMP
Cyclic via adenosine monophosphate Signal binding to GPCR activates G protein to bind GTP causing dissociation One type of subunit binds to adenylyl cyclase stimulating synthesis of cAMP One effect of cAMP is to activate protein kinase A (PKA) Activated catalytic PKA subunits phosphorylates specific cellular proteins When signaling molecules no longer produced, eventually effects of PKA reversed 30
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cAMP has 2 advantages
1.
2.
Signal amplification binding of signal to single receptor can cause the synthesis of many cAMP that activate PKA, each PKA can phosphorylate many proteins Speed in one experiment a substantial amount of cAMP was made within 20 seconds after addition of signal
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Signal transduction via Ca2+
Cells maintain a very large Ca2+ gradient 2 types of calcium pumps When calcium channels open, influx of Ca2+ acts as a second messenger Plants- phototropism, opening and closing of stomata, gravitropism Animals- nerve transmission, muscle contraction, secretion of digestive enzymes
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Signal transduction via diacylglycerol and inositol triphosphate
Second way for an activated G protein to influence signal transduction pathway A subunit can activate phospholipase C Diacylglycerol and inositol triphosphate made from plasma membrane phospholipid Ca2+ channels in ER open Variety of effect of Ca2+ on cell behavior
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Epinephrine
Different effects throughout the body Heart muscle cells
controlled by Ca2+ Ca2+ stored in sarcoplasmic reticulum Ca2+ binds to troponin leading to muscle contraction Dropping Ca2+ causes muscle to relax
Contraction
Phospholamban activates Ca2+ pump
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Epinephrine increases heart rate Activates adenylyl cyclase which produces cAMP cAMP activates PKA to phosphorylate troponin and phospholamban Enhances troponin Ca2+ binding and increases rate of contraction Enhances Ca2+ pump function and increases rate of relaxation
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A cell's response to signaling molecules depends on the proteins it makes
One hormone causes different effects in different cell types Differential gene expression- all cells contain the same genome but only express particular parts Can effect cellular response in a variety of ways
Receptor
not expressed, different receptors for same signal, different affinities for signal, signal transduction pathways different, protein expression different
Regulation of cell cycle
G1 first gap S synthesis of DNA Interphase G2 second gap M mitosis and cytokinesis
G0 substitute for G1 for cells postponing division or never dividing again
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During G1, cell decides to divide Accumulates molecular changes that cause progression through the cell cycle Passes restriction point where cell is committed to enter S phase Chromosomes replicate during S phase forming sister chromatids
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During G2, cell synthesizes proteins needed during mitosis and cytokinesis M phase mitosis
Divide
one cell nucleus into two
Cyokinesis, division of cytoplasm, follows in most cases
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Decision to divide
Environmental conditions primarily influence unicellular organisms Multicellular organisms are more complex Rely on signaling molecules to coordinate cell division Cytokinins promote cell division in plants Growth factors stimulate certain cells to grow in animals
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Epidermal Growth Factor (EGF)
Simplified signal transduction pathway EGF secreted by endocrine cells and stimulates skin cells to divide Growth factors (like EGF) cause rapid increase in the expression of many genes in mammals Mutations causing proteins in these pathways to become hyperactive can result in uncontrolled cell division (cancer)
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Cyclins or cyclin-dependent kinases (cdks) responsible for advancing a cell through the phases of the cell cycle Kinases controlling cell cycle must bind to a cyclin to be active
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3 critical regulatory points or checkpoints in eukaryotes
G1
checkpoint (restriction point) G2 checkpoint Metaphase checkpoint
Checkpoint proteins act as sensors to determine if the cell is in proper condition to divide Cell cycle will be delayed or until problems fixed or prevents division entirely Loss of checkpoint function can lead to mutation and cancer 56
Masui and Markert's study of oocyte maturation led to the identification of cyclin and cyclin-dependent kinase
Frog oocytes are dormant in G2 Progesterone makes oocytes progress to M Progesterone must be affecting triggers to progress to M 3 groups of donor oocytes
Progesterone
for 2 hours Progesterone for 12 hours No progesterone
Inject donor oocyte cytosol into recipient oocytes Only 12 hour donor caused progression Maturation Promoting Factor (MPF) is mitotic cyclin and cyclin-dependent kinase
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