1. CHAPTER 9 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.

2. 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

3. 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

4. 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

5. Why do cells need to respond to signals?
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

7. 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

9. Signals relayed between cells
Direct intercellular signaling
Cell junctions allow signaling molecules to pass from one cell to another
Contact-dependent signaling
Some molecules are bound to the surface of cells and serve as signals to cell coming in contact with them
Autocrine signaling
Cells secrete signaling molecules that bind to their own cell surface or neighboring cells of the same type

10. Paracrine signaling Endocrine signaling
Signal does not affect cell secreting the signal but does influence cells in close proximity (synaptic signaling)
Endocrine signaling
Signals (hormones) travel long distances and are usually longer lasting

12. 3 stages of cell signaling
Receptor activation
Signaling molecule binds to receptor
Signal transduction
Activated receptor stimulates sequence of changes- signal transduction pathway
Cellular response
Several different responses
Alter activity of 1 or more enzymes
Alter structural protein function
Change gene expression

14. Ligand Signaling molecule
Binds noncovalently to receptor with high degree of specificity
Binding and release between receptor and ligand relatively rapid
Ligands alter receptor structure- conformational change
Hormone-receptor complex is an activated receptor that can initiate a cellular response

16. Cell surface receptors
Enzyme-linked receptors
Found in all living species
Extracellular domain binds signal
Causes intracellular domain to become functional catalyst
Most are protein kinases

18. 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

20. 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

22. 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

24. 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

26. Cellular response Two-component regulatory system Sensor kinase
Bacteria, fungi and plants (not animals)
Sensor kinase
Enzyme-linked receptor
Hydrolyzes ATP and phosphorylates
Phosphate group transferred to response regulator
Response regulator
Regulates expression of many genes

27. 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

29. 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

30. Signal transduction via cAMP
Cyclic 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

33. cAMP has 2 advantages
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

36. 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

38. 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

40. Epinephrine Different effects throughout the body Heart muscle cells
Contraction controlled by Ca2+
Ca2+ stored in sarcoplasmic reticulum
Ca2+ binds to troponin leading to muscle contraction
Dropping Ca2+ causes muscle to relax
Phospholamban activates Ca2+ pump

43. 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

45. One hormone causes different effects in different cell types
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

46. 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

48. 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

50. Cyokinesis, division of cytoplasm, follows in most cases
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

51. 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

52. 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)

54. 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

56. 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

57. Frog oocytes are dormant in G2
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