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Transcript of Chapter 11 Cell Communication. Overview: The Cellular Internet Cell-to-cell communication is...
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Chapter 11
Cell Communication
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Overview: The Cellular Internet
• Cell-to-cell communication is essential for multicellular organisms
• Biologists have discovered some universal mechanisms of cellular regulation
• The combined effects of multiple signals determine cell response
• For example, the dilation of blood vessels is controlled by multiple molecules
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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You should now be able to:
1. Describe the nature of a ligand-receptor interaction and state how such interactions initiate a signal-transduction system
2. Compare and contrast G protein-coupled receptors, tyrosine kinase receptors, and ligand-gated ion channels
3. List two advantages of a multistep pathway in the transduction stage of cell signaling
4. Explain how an original signal molecule can produce a cellular response when it may not even enter the target cell
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5. Define the term second messenger; briefly describe the role of these molecules in signaling pathways
6. Explain why different types of cells may respond differently to the same signal molecule
7. Describe the role of apoptosis in normal development and degenerative disease in vertebrates
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Fig. 11-5ab
Local signaling
Target cell
Secretoryvesicle
Secretingcell
Local regulatordiffuses throughextracellular fluid
(a) Paracrine signaling (b) Synaptic signaling
Target cellis stimulated
Neurotransmitter diffuses across synapse
Electrical signalalong nerve celltriggers release ofneurotransmitter
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Fig. 11-5c
Long-distance signaling
Endocrine cell Bloodvessel
Hormone travelsin bloodstreamto target cells
Targetcell
(c) Hormonal signaling
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The Three Stages of Cell Signaling: A Preview
• Earl W. Sutherland discovered how the hormone epinephrine acts on cells
• Sutherland suggested that cells receiving signals went through three processes:– Reception– Transduction– Response
Animation: Overview of Cell Signaling
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Concept 11.2: Reception: A signal molecule binds to a receptor protein, causing it to change shape
• The binding between a signal molecule (ligand) and receptor is highly specific
• A shape change in a receptor is often the initial transduction of the signal
• Most signal receptors are plasma membrane proteins
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Fig. 11-6-1
Reception1
EXTRACELLULARFLUID
Signalingmolecule
Plasma membrane
CYTOPLASM
1
Receptor
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Fig. 11-6-2
1
EXTRACELLULARFLUID
Signalingmolecule
Plasma membrane
CYTOPLASM
Transduction2
Relay molecules in a signal transduction pathway
Reception1
Receptor
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Fig. 11-6-3
EXTRACELLULARFLUID
Plasma membrane
CYTOPLASM
Receptor
Signalingmolecule
Relay molecules in a signal transduction pathway
Activationof cellularresponse
Transduction Response2 3Reception1
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Receptors in the Plasma Membrane
• Most water-soluble signal molecules bind to specific sites on receptor proteins in the plasma membrane
• There are three main types of membrane receptors:– G protein-coupled receptors– Receptor tyrosine kinases– Ion channel receptors
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• A G protein-coupled 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
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Fig. 11-7b
G protein-coupledreceptor
Plasmamembrane
EnzymeG protein(inactive)
GDP
CYTOPLASM
Activatedenzyme
GTP
Cellular response
GDP
P i
Activatedreceptor
GDP GTP
Signaling moleculeInactiveenzyme
1 2
3 4
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• Receptor tyrosine kinases are membrane receptors that attach phosphates to tyrosines
• A receptor tyrosine kinase can trigger multiple signal transduction pathways at once
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Fig. 11-7c
Signalingmolecule (ligand)
Ligand-binding site
Helix
TyrosinesTyr
Tyr
Tyr
Tyr
Tyr
Tyr
Receptor tyrosinekinase proteins
CYTOPLASM
Signalingmolecule
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Dimer
Activated relayproteins
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
PPP
P
PP
Cellularresponse 1
Cellularresponse 2
Inactiverelay proteins
Activated tyrosinekinase regions
Fully activated receptortyrosine kinase
6 6 ADPATP
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
PPP
PPP
1 2
3 4
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• A ligand-gated 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
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Fig. 11-7d
Signalingmolecule(ligand)
Gateclosed Ions
Ligand-gatedion channel receptor
Plasmamembrane
Gate open
Cellularresponse
Gate closed3
2
1
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Intracellular Receptors
• Some receptor proteins are intracellular, found in the cytosol or nucleus of target cells
• 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
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Fig. 11-8-1
Hormone(testosterone)
Receptorprotein
Plasmamembrane
EXTRACELLULARFLUID
DNA
NUCLEUS
CYTOPLASM
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Fig. 11-8-2
Receptorprotein
Hormone(testosterone)
EXTRACELLULARFLUID
Plasmamembrane
Hormone-receptorcomplex
DNA
NUCLEUS
CYTOPLASM
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Fig. 11-8-3
Hormone(testosterone)
EXTRACELLULARFLUID
Receptorprotein
Plasmamembrane
Hormone-receptorcomplex
DNA
NUCLEUS
CYTOPLASM
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Fig. 11-8-4
Hormone(testosterone)
EXTRACELLULARFLUID
PlasmamembraneReceptor
protein
Hormone-receptorcomplex
DNA
mRNA
NUCLEUS
CYTOPLASM
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Fig. 11-8-5
Hormone(testosterone)
EXTRACELLULARFLUID
Receptorprotein
Plasmamembrane
Hormone-receptorcomplex
DNA
mRNA
NUCLEUS New protein
CYTOPLASM
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Concept 11.3: Transduction: Cascades of molecular interactions relay signals from receptors to target
molecules in the cell
• Signal transduction usually involves multiple steps
• Multistep pathways can amplify a signal: A few molecules can produce a large cellular response
• Multistep pathways provide more opportunities for coordination and regulation of the cellular response
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Protein Phosphorylation and Dephosphorylation
• In many pathways, the signal is transmitted by a cascade of protein phosphorylations
• Protein kinases transfer phosphates from ATP to protein, a process called phosphorylation
• Protein phosphatases remove the phosphates from proteins, a process called dephosphorylation
• This phosphorylation and dephosphorylation system acts as a molecular switch, turning activities on and off
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Fig. 11-9
Signaling molecule
ReceptorActivated relaymolecule
Inactiveprotein kinase
1 Activeproteinkinase
1
Inactiveprotein kinase
2
ATPADP Active
proteinkinase
2
P
PPP
Inactiveprotein kinase
3
ATPADP Active
proteinkinase
3
P
PPP
i
ATPADP P
ActiveproteinPP
P i
Inactiveprotein
Cellularresponse
Phosphorylation cascadei
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Small Molecules and Ions as Second Messengers
• The extracellular signal molecule that binds to the receptor is a pathway’s “first messenger”
• Second messengers are small, nonprotein, water-soluble molecules or ions that spread throughout a cell by diffusion
• Second messengers participate in pathways initiated by G protein-coupled receptors and receptor tyrosine kinases
• Cyclic AMP and calcium ions are common second messengers
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Cyclic AMP
• 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
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Adenylyl cyclase
Fig. 11-10
Pyrophosphate
P P i
ATP cAMP
Phosphodiesterase
AMP
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• Many signal molecules trigger formation of cAMP
• Other components of cAMP pathways are G proteins, G protein-coupled receptors, and protein kinases
• cAMP usually activates protein kinase A, which phosphorylates various other proteins
• Further regulation of cell metabolism is provided by G-protein systems that inhibit adenylyl cyclase
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First messengerFig. 11-11
G proteinAdenylylcyclase
GTP
ATPcAMP
Secondmessenger
Proteinkinase A
G protein-coupledreceptor
Cellular responses
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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
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EXTRACELLULARFLUID
Fig. 11-12
ATP
Nucleus
Mitochondrion
Ca2+ pump
Plasmamembrane
CYTOSOL
Ca2+
pumpEndoplasmicreticulum (ER)
Ca2+
pumpATP
Key
High [Ca2+]Low [Ca2+]
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• A signal relayed by a signal transduction pathway may trigger an increase in calcium in the cytosol
• Pathways leading to the release of calcium involve inositol triphosphate (IP3) and diacylglycerol (DAG) as additional second messengers
Animation: Signal Transduction Pathways
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Fig. 11-13-1
EXTRA-CELLULARFLUID
Signaling molecule(first messenger)
G protein
GTP
G protein-coupledreceptor Phospholipase C PIP2
IP3
DAG
(second messenger)
IP3-gatedcalcium channel
Endoplasmicreticulum (ER) Ca2+
CYTOSOL
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Fig. 11-13-2
G protein
EXTRA-CELLULARFLUID
Signaling molecule(first messenger)
G protein-coupledreceptor Phospholipase C PIP2
DAG
IP3(second messenger)
IP3-gatedcalcium channel
Endoplasmicreticulum (ER) Ca2+
CYTOSOL
Ca2+
(secondmessenger)
GTP
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Fig. 11-13-3
G protein
EXTRA-CELLULARFLUID
Signaling molecule(first messenger)
G protein-coupledreceptor Phospholipase C PIP2
DAG
IP3(second messenger)
IP3-gatedcalcium channel
Endoplasmicreticulum (ER) Ca2+
CYTOSOL
Variousproteinsactivated
Cellularresponses
Ca2+
(secondmessenger)
GTP
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Fig. 11-14
Growth factor
Receptor
Phosphorylationcascade
Reception
Transduction
Activetranscriptionfactor
ResponseP
Inactivetranscriptionfactor
CYTOPLASM
DNA
NUCLEUS mRNA
Gene
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Fig. 11-15
Reception
Transduction
Response
Binding of epinephrine to G protein-coupled receptor (1 molecule)
Inactive G protein
Active G protein (102 molecules)
Inactive adenylyl cyclaseActive adenylyl cyclase (102)
ATPCyclic AMP (104)
Inactive protein kinase AActive protein kinase A (104)
Inactive phosphorylase kinaseActive phosphorylase kinase (105)
Inactive glycogen phosphorylase
Active glycogen phosphorylase (106)
GlycogenGlucose-1-phosphate
(108 molecules)
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Fig. 11-16a
RESULTS
Wild-type (shmoos) ∆Fus3 ∆formin
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Fig. 11-16b
CONCLUSION
Matingfactor G protein-coupled
receptor
GDP GTP
Phosphory- lation cascade
Shmoo projectionforming
Fus3
Fus3 Fus3
Formin Formin
P
P
P
ForminP
Actinsubunit
Microfilament
1
2
3
4
5
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The Specificity of Cell Signaling and Coordination of the Response
• Different kinds of cells have different collections of proteins
• These different proteins allow cells to detect and respond to different signals
• Even the same signal can have different effects in cells with different proteins and pathways
• Pathway branching and “cross-talk” further help the cell coordinate incoming signals
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Fig. 11-17a
Signalingmolecule
Receptor
Relaymolecules
Response 1
Cell A. Pathway leadsto a single response.
Cell B. Pathway branches,leading to two responses.
Response 2 Response 3
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Fig. 11-17b
Response 4 Response 5
Activationor inhibition
Cell C. Cross-talk occursbetween two pathways.
Cell D. Different receptorleads to a different response.
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Signaling Efficiency: Scaffolding Proteins and Signaling Complexes
• Scaffolding proteins are large relay proteins to which other relay proteins are attached
• Scaffolding proteins can increase the signal transduction efficiency by grouping together different proteins involved in the same pathway
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Fig. 11-18
Signalingmolecule
Receptor
Scaffoldingprotein
Plasmamembrane
Threedifferentproteinkinases
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Signaling Efficiency: Scaffolding Proteins and Signaling Complexes
• Scaffolding proteins are large relay proteins to which other relay proteins are attached
• Scaffolding proteins can increase the signal transduction efficiency by grouping together different proteins involved in the same pathway
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Fig. 11-18
Signalingmolecule
Receptor
Scaffoldingprotein
Plasmamembrane
Threedifferentproteinkinases
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Concept 11.5: Apoptosis (programmed cell death) integrates multiple cell-signaling pathways
• Apoptosis is programmed or controlled cell suicide
• A cell is chopped and packaged into vesicles that are digested by scavenger cells
• Apoptosis prevents enzymes from leaking out of a dying cell and damaging neighboring cells
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Fig. 11-19
2 µm
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Fig. 11-20a
Ced-9protein (active)inhibits Ced-4activity
Mitochondrion
Ced-4 Ced-3Receptorfor death-signalingmolecule
Inactive proteins
(a) No death signal
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Fig. 11-20b
(b) Death signal
Death-signalingmolecule
Ced-9(inactive)
Cellformsblebs
ActiveCed-4
ActiveCed-3
Activationcascade
Otherproteases
Nucleases
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Apoptotic Pathways and the Signals That Trigger Them
• Caspases are the main proteases (enzymes that cut up proteins) that carry out apoptosis
• Apoptosis can be triggered by:– An extracellular death-signaling ligand – DNA damage in the nucleus– Protein misfolding in the endoplasmic reticulum
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Apoptosis
• Apoptosis (1972)– Greek word “falling off”
• Built-in (programmed)mechanism)
• or self-destruction-suicide
• Type of programmedcell death based uponmorphological features
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Jacobson et al (1997) Cell, Vol. 88, 347–354,
Apoptosis plays in an important role in normal developmental processes
Studies on the development of the nervous system showed that in the process of assembling sensory fields, neurons are eliminated by orderly cell death in order to tailor sensory input to environmental stimuli (elimination or transplantation of limbs as key examples).
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Programmed cell death during development. Programmed cell death is involved in forming structures such as the digits of the hand (a), deleting structures such as nearly all of an insect's larval components (b), controlling cell
numbers in, for example, the nervous system (c) and eliminating abnormal cells such as those that harbour mutations (d).
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Apoptosis is also important in the development of the nervous system
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• Apoptosis evolved early in animal evolution and is essential for the development and maintenance of all animals
• Apoptosis may be involved in some diseases (for example, Parkinson’s and Alzheimer’s); interference with apoptosis may contribute to some cancers
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Fig. 11-21
Interdigital tissue 1 mm
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Fig. 11-UN1
Reception Transduction Response
Receptor
Relay molecules
Signalingmolecule
Activationof cellularresponse
1 2 3
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Question????
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Chapter 12
The Cell Cycle
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You should now be able to:
1. Describe the structural organization of the prokaryotic genome and the eukaryotic genome
2. List the phases of the cell cycle; describe the sequence of events during each phase
3. List the phases of mitosis and describe the events characteristic of each phase
4. Draw or describe the mitotic spindle, including centrosomes, kinetochore microtubules, nonkinetochore microtubules, and asters
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5. Compare cytokinesis in animals and plants6. Describe the process of binary fission in
bacteria and explain how eukaryotic mitosis may have evolved from binary fission
7. Explain how the abnormal cell division of cancerous cells escapes normal cell cycle controls
8. Distinguish between benign, malignant, and metastatic tumors
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Overview: The Key Roles of Cell Division
• The ability of organisms to reproduce best distinguishes living things from nonliving matter
• The continuity of life is based on the reproduction of cells, or cell division
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Fig. 12-1
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Fig. 12-2a
100 µm
(a) Reproduction
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Fig. 12-2b
200 µm
(b) Growth and development
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Fig. 12-2c
20 µm
(c) Tissue renewal
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Fig. 12-40.5 µm Chromosomes
Chromosomeduplication(including DNAsynthesis)
Chromo-some arm
Centromere
Sisterchromatids
DNA molecules
Separation ofsister chromatids
Centromere
Sister chromatids
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Phases of the Cell Cycle• The cell cycle consists of
– Mitotic (M) phase (mitosis and cytokinesis)– Interphase (cell growth and copying of
chromosomes in preparation for cell division)
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Fig. 12-5
S(DNA synthesis)
MITOTIC(M) PHASE
Mito
sis
Cytokinesis
G1
G2
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• Mitosis is conventionally divided into five phases:– Prophase– Prometaphase– Metaphase– Anaphase– Telophase
• Cytokinesis is well underway by late telophase
BioFlix: Mitosis
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Prophase
Fig. 12-6a
PrometaphaseG2 of Interphase
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Fig. 12-6b
PrometaphaseProphaseG2 of Interphase
Nonkinetochoremicrotubules
Fragmentsof nuclearenvelope
Aster CentromereEarly mitoticspindle
Chromatin(duplicated)
Centrosomes(with centriolepairs)
Nucleolus Nuclearenvelope
Plasmamembrane
Chromosome, consistingof two sister chromatids
Kinetochore Kinetochoremicrotubule
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Fig. 12-6c
Metaphase Anaphase Telophase and Cytokinesis
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Fig. 12-6d
Metaphase Anaphase Telophase and Cytokinesis
Cleavagefurrow
Nucleolusforming
Metaphaseplate
Centrosome atone spindle pole
SpindleDaughterchromosomes
Nuclearenvelopeforming
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Cleavage furrow
Fig. 12-9a
100 µm
Daughter cells
(a) Cleavage of an animal cell (SEM)
Contractile ring ofmicrofilaments
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Fig. 12-9b
Daughter cells
(b) Cell plate formation in a plant cell (TEM)
Vesiclesformingcell plate
Wall ofparent cell
New cell wallCell plate
1 µm
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Fig. 12-10
Chromatincondensing
Metaphase Anaphase TelophasePrometaphase
Nucleus
Prophase1 2 3 54
Nucleolus Chromosomes Cell plate10 µm
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Fig. 11-1