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Chapter 11 Cell Communication.

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Presentation on theme: "Chapter 11 Cell Communication."— Presentation transcript:

1 Chapter 11 Cell Communication

2 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

3 Cell- cell interactions

4 You should now be able to:
Describe the nature of a ligand-receptor interaction and state how such interactions initiate a signal-transduction system Compare and contrast G protein-coupled receptors, tyrosine kinase receptors, and ligand-gated ion channels List two advantages of a multistep pathway in the transduction stage of cell signaling Explain how an original signal molecule can produce a cellular response when it may not even enter the target cell Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

5 Define the term second messenger; briefly describe the role of these molecules in signaling pathways
Explain why different types of cells may respond differently to the same signal molecule Describe the role of apoptosis in normal development and degenerative disease in vertebrates Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

6 (a) Paracrine signaling (b) Synaptic signaling
Fig. 11-5ab Local signaling Target cell Electrical signal along nerve cell triggers release of neurotransmitter Neurotransmitter diffuses across synapse Secreting cell Secretory vesicle Figure 11.5 Local and long-distance cell communication in animals Local regulator diffuses through extracellular fluid Target cell is stimulated (a) Paracrine signaling (b) Synaptic signaling

7 Long-distance signaling
Fig. 11-5c Long-distance signaling Endocrine cell Blood vessel Hormone travels in bloodstream to target cells Figure 11.5 Local and long-distance cell communication in animals Target cell (c) Hormonal signaling

8 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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

9 Most signal receptors are plasma membrane proteins
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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

10 Plasma membrane 1 Reception Receptor Signaling molecule 1
Fig EXTRACELLULAR FLUID CYTOPLASM Plasma membrane 1 1 Reception Receptor Figure 11.6 Overview of cell signaling Signaling molecule

11 Plasma membrane 1 Reception Transduction Receptor Signaling molecule 1
Fig EXTRACELLULAR FLUID CYTOPLASM Plasma membrane 1 1 Reception 2 Transduction Receptor Relay molecules in a signal transduction pathway Figure 11.6 Overview of cell signaling Signaling molecule

12 Plasma membrane 1 Reception Transduction Response Receptor Activation
Fig EXTRACELLULAR FLUID CYTOPLASM Plasma membrane 1 Reception 2 Transduction 3 Response Receptor Activation of cellular response Relay molecules in a signal transduction pathway Figure 11.6 Overview of cell signaling Signaling molecule

13 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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

14 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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

15 Figure 11.7 Membrane receptors—G protein-coupled receptors, part 2
Fig. 11-7b Plasma membrane G protein-coupled receptor Inactive enzyme Activated receptor Signaling molecule GDP G protein (inactive) Enzyme GDP GTP CYTOPLASM 1 2 Activated enzyme Figure 11.7 Membrane receptors—G protein-coupled receptors, part 2 GTP GDP P i Cellular response 3 4

16 Receptor tyrosine kinases are membrane receptors that attach phosphates to tyrosines
A receptor tyrosine kinase can trigger multiple signal transduction pathways at once Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

17 Fully activated receptor tyrosine kinase
Fig. 11-7c Signaling molecule (ligand) Ligand-binding site Signaling molecule  Helix Tyr Tyr Tyrosines Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Receptor tyrosine kinase proteins Dimer CYTOPLASM 1 2 Activated relay proteins Figure 11.7 Membrane receptors—receptor tyrosine kinases Cellular response 1 Tyr Tyr P Tyr Tyr P Tyr Tyr P P Tyr Tyr P Tyr Tyr P Tyr Tyr P P Cellular response 2 Tyr Tyr P Tyr Tyr P Tyr P Tyr P 6 ATP 6 ADP Activated tyrosine kinase regions Fully activated receptor tyrosine kinase Inactive relay proteins 3 4

18 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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

19 1 Signaling molecule (ligand) Gate closed Ions Plasma membrane
Fig. 11-7d 1 Signaling molecule (ligand) Gate closed Ions Plasma membrane Ligand-gated ion channel receptor 2 Gate open Cellular response Figure 11.7 Membrane receptors—ion channel receptors 3 Gate closed

20 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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

21 Hormone (testosterone) Plasma membrane Receptor protein DNA NUCLEUS
Fig Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein DNA Figure 11.8 Steroid hormone interacting with an intracellular receptor NUCLEUS CYTOPLASM

22 Hormone (testosterone) Plasma membrane Receptor protein Hormone-
Fig Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein Hormone- receptor complex DNA Figure 11.8 Steroid hormone interacting with an intracellular receptor NUCLEUS CYTOPLASM

23 Hormone (testosterone) Plasma membrane Receptor protein Hormone-
Fig Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein Hormone- receptor complex DNA Figure 11.8 Steroid hormone interacting with an intracellular receptor NUCLEUS CYTOPLASM

24 Hormone (testosterone) Plasma membrane Receptor protein Hormone-
Fig Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein Hormone- receptor complex DNA Figure 11.8 Steroid hormone interacting with an intracellular receptor mRNA NUCLEUS CYTOPLASM

25 Hormone (testosterone) Plasma membrane Receptor protein Hormone-
Fig Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein Hormone- receptor complex DNA Figure 11.8 Steroid hormone interacting with an intracellular receptor mRNA NUCLEUS New protein CYTOPLASM

26 Signal transduction usually involves multiple steps
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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

27 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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

28 Phosphorylation cascade
Fig. 11-9 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 Figure 11.9 A phosphorylation cascade 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

29 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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

30 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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

31 Figure 11.10 Cyclic AMP Adenylyl cyclase Phosphodiesterase
Pyrophosphate P P i ATP cAMP AMP Figure Cyclic AMP

32 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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

33 First messenger Adenylyl cyclase G protein GTP G protein-coupled
Fig First messenger Adenylyl cyclase G protein G protein-coupled receptor GTP ATP Second messenger cAMP Figure cAMP as second messenger in a G-protein-signaling pathway Protein kinase A Cellular responses

34 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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

35 EXTRACELLULAR FLUID Plasma membrane Ca2+ pump ATP Mitochondrion
Fig EXTRACELLULAR FLUID Plasma membrane Ca2+ pump ATP Mitochondrion Nucleus CYTOSOL Ca2+ pump Endoplasmic reticulum (ER) Figure The maintenance of calcium ion concentrations in an animal cell Ca2+ pump ATP Key High [Ca2+] Low [Ca2+]

36 Animation: Signal Transduction Pathways
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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

37 EXTRA- CELLULAR FLUID Signaling molecule (first messenger) G protein
Fig 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 Calcium and IP3 in signaling pathways Endoplasmic reticulum (ER) Ca2+ CYTOSOL

38 EXTRA- CELLULAR FLUID Signaling molecule (first messenger) G protein
Fig 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 Calcium and IP3 in signaling pathways Endoplasmic reticulum (ER) Ca2+ Ca2+ (second messenger) CYTOSOL

39 EXTRA- CELLULAR FLUID Signaling molecule (first messenger) G protein
Fig 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 Calcium and IP3 in signaling pathways Endoplasmic reticulum (ER) Various proteins activated Cellular responses Ca2+ Ca2+ (second messenger) CYTOSOL

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

41 Glucose-1-phosphate (108 molecules)
Fig Reception Binding of epinephrine to G protein-coupled receptor (1 molecule) Transduction Inactive G protein Active G protein (102 molecules) Inactive adenylyl cyclase Active adenylyl cyclase (102) ATP Cyclic AMP (104) Inactive protein kinase A Active protein kinase A (104) Figure Cytoplasmic response to a signal: the stimulation of glycogen breakdown by epinephrine Inactive phosphorylase kinase Active phosphorylase kinase (105) Inactive glycogen phosphorylase Active glycogen phosphorylase (106) Response Glycogen Glucose-1-phosphate (108 molecules)

42 Wild-type (shmoos) ∆Fus3 ∆formin RESULTS
Fig a RESULTS Figure How do signals induce directional cell growth in yeast? Wild-type (shmoos) ∆Fus3 ∆formin

43 CONCLUSION Mating factor Shmoo projection forming G protein-coupled
Fig b CONCLUSION Mating factor 1 Shmoo projection forming G protein-coupled receptor Formin P Fus3 Actin subunit GTP P GDP 2 Phosphory- lation cascade Formin Formin P 4 Figure How do signals induce directional cell growth in yeast? Microfilament Fus3 Fus3 P 5 3

44 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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

45 Cell B. Pathway branches, leading to two responses.
Fig a Signaling molecule Receptor Relay molecules Figure The specificity of cell signaling Response 1 Response 2 Response 3 Cell A. Pathway leads to a single response. Cell B. Pathway branches, leading to two responses.

46 Cell C. Cross-talk occurs between two pathways.
Fig b Activation or inhibition Figure The specificity of cell signaling Response 4 Response 5 Cell C. Cross-talk occurs between two pathways. Cell D. Different receptor leads to a different response.

47 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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

48 Signaling Plasma molecule membrane Receptor Three different protein
Fig Signaling molecule Plasma membrane Receptor Three different protein kinases Figure A scaffolding protein Scaffolding protein

49 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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

50 Signaling Plasma molecule membrane Receptor Three different protein
Fig Signaling molecule Plasma membrane Receptor Three different protein kinases Figure A scaffolding protein Scaffolding protein

51 Apoptosis is programmed or controlled cell suicide
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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

52 Fig Figure Apoptosis of human white blood cells 2 µm

53 Ced-9 protein (active) inhibits Ced-4 activity Mitochondrion Ced-4
Fig a Ced-9 protein (active) inhibits Ced-4 activity Mitochondrion Figure Molecular basis of apoptosis in C. elegans Ced-4 Ced-3 Receptor for death- signaling molecule Inactive proteins (a) No death signal

54 Ced-9 (inactive) Cell forms blebs Death- signaling molecule Active
Fig b Ced-9 (inactive) Cell forms blebs Death- signaling molecule Active Ced-4 Active Ced-3 Other proteases Nucleases Figure Molecular basis of apoptosis in C. elegans Activation cascade (b) Death signal

55 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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

56

57 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). Apoptosis plays in an important role in normal developmental processes Jacobson et al (1997) Cell, Vol. 88, 347–354,

58 Programmed cell death during development
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).

59 Apoptosis is also important in the development of the nervous system

60 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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

61 Interdigital tissue 1 mm
Fig Interdigital tissue 1 mm Figure Effect of apoptosis during paw development in the mouse

62

63 Reception Transduction Response Receptor Activation of cellular
Fig. 11-UN1 1 Reception 2 Transduction 3 Response Receptor Activation of cellular response Relay molecules Signaling molecule

64 Question????

65 Chapter 12 The Cell Cycle

66 You should now be able to:
Describe the structural organization of the prokaryotic genome and the eukaryotic genome List the phases of the cell cycle; describe the sequence of events during each phase List the phases of mitosis and describe the events characteristic of each phase Draw or describe the mitotic spindle, including centrosomes, kinetochore microtubules, nonkinetochore microtubules, and asters Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

67 Compare cytokinesis in animals and plants
Describe the process of binary fission in bacteria and explain how eukaryotic mitosis may have evolved from binary fission Explain how the abnormal cell division of cancerous cells escapes normal cell cycle controls Distinguish between benign, malignant, and metastatic tumors Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

68 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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

69 Figure 12.1 How do a cell’s chromosomes change during cell division?

70 100 µm (a) Reproduction Figure 12.2 The functions of cell division
Fig. 12-2a 100 µm Figure 12.2 The functions of cell division (a) Reproduction

71 (b) Growth and development
Fig. 12-2b 200 µm Figure 12.2 The functions of cell division (b) Growth and development

72 20 µm (c) Tissue renewal Figure 12.2 The functions of cell division
Fig. 12-2c 20 µm Figure 12.2 The functions of cell division (c) Tissue renewal

73 0.5 µm Chromosomes DNA molecules Chromo- some arm Chromosome
Fig. 12-4 0.5 µm Chromosomes DNA molecules Chromo- some arm Chromosome duplication (including DNA synthesis) Centromere Sister chromatids Figure 12.4 Chromosome duplication and distribution during cell division Separation of sister chromatids Centromere Sister chromatids

74 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) Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

75 S (DNA synthesis) G1 Cytokinesis G2 Mitosis
Fig. 12-5 INTERPHASE S (DNA synthesis) G1 Cytokinesis G2 Mitosis Figure 12.5 The cell cycle MITOTIC (M) PHASE

76 Mitosis is conventionally divided into five phases:
Prophase Prometaphase Metaphase Anaphase Telophase Cytokinesis is well underway by late telophase For the Cell Biology Video Myosin and Cytokinesis, go to Animation and Video Files. BioFlix: Mitosis Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

77 G2 of Interphase Prophase Prometaphase
Fig. 12-6a Figure 12.6 The mitotic division of an animal cell G2 of Interphase Prophase Prometaphase

78 Chromosome, consisting of two sister chromatids
Fig. 12-6b G2 of Interphase Prophase Prometaphase Centrosomes (with centriole pairs) Chromatin (duplicated) Early mitotic spindle Aster Centromere Fragments of nuclear envelope Nonkinetochore microtubules Figure 12.6 The mitotic division of an animal cell Nucleolus Nuclear envelope Plasma membrane Chromosome, consisting of two sister chromatids Kinetochore Kinetochore microtubule

79 Telophase and Cytokinesis
Fig. 12-6c Figure 12.6 The mitotic division of an animal cell Metaphase Anaphase Telophase and Cytokinesis

80 Telophase and Cytokinesis
Fig. 12-6d Metaphase Anaphase Telophase and Cytokinesis Metaphase plate Cleavage furrow Nucleolus forming Figure 12.6 The mitotic division of an animal cell Daughter chromosomes Nuclear envelope forming Spindle Centrosome at one spindle pole

81 (a) Cleavage of an animal cell (SEM)
Fig. 12-9a 100 µm Cleavage furrow Figure 12.9a Cytokinesis in animal and plant cells Contractile ring of microfilaments Daughter cells (a) Cleavage of an animal cell (SEM)

82 (b) Cell plate formation in a plant cell (TEM)
Fig. 12-9b Vesicles forming cell plate Wall of parent cell 1 µm Cell plate New cell wall Figure 12.9b Cytokinesis in animal and plant cells Daughter cells (b) Cell plate formation in a plant cell (TEM)

83 10 µm Nucleus Chromatin condensing Nucleolus Chromosomes Cell plate
Fig Nucleus Chromatin condensing 10 µm Nucleolus Chromosomes Cell plate Figure Mitosis in a plant cell 1 Prophase 2 Prometaphase 3 Metaphase 4 Anaphase 5 Telophase

84 Fig. 11-1 Figure 11.1 How do the effects of Viagra (multicolored) result from its inhibition of a signaling-pathway enzyme (purple)?


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