1. Chapter 11 Cell Communication

2. Why Do Cells Need to Communicate? Hormones – Feedback Mechanisms Mitosis – Start/Stop Division Muscle Contraction - Thermogenics Nervous (Action Potential) - Propagation Apoptosis – Cell Suicide (End of Life Cycle) Gene Expression Immunity – Activation of T & B Cells Cancer – Angiogensis & Growth Factors

3. Local signaling Target cell Secreting cell Secretory vesicle Local regulator diffuses through extracellular fluid (a) Paracrine signaling(b) Synaptic signaling Target cell is stimulated Neurotransmitter diffuses across synapse Electrical signal along nerve cell triggers release of neurotransmitter Long-distance signaling Endocrine cell Blood vessel Hormone travels in bloodstream to target cells Target cell (c) Hormonal signaling

4. Fig. 11-4 Plasma membranes Gap junctions between animal cells (a) Cell junctions Plasmodesmata between plant cells (b) Cell-cell recognition

5. Fig. 7-9 (a) Transport ATP (b) Enzymatic activity Enzymes (c) Signal transduction Signal transduction Signaling molecule Receptor (d) Cell-cell recognition Glyco- protein (e) Intercellular joining (f) Attachment to the cytoskeleton and extracellular matrix (ECM)

6. Negative Feedback Mechanisms

7. Positive Feedback Mechanisms

8. Hormones: Vital Roles Control several major processes –Reproduction –Growth and development –Mobilization of body defenses –Maintenance of homeostasis –Regulation of metabolism Monitored by Negative/Positive Feedback Mechanisms

9. Endocrine Endocrine - Hormones secreted through bloodstream

10. HYPOTHALAMUS The hypothalamus is an area of the brain that produces the "controlling" hormones. These hormones regulate body processes such as metabolism, and control the release of hormones from glands like the thyroid, the adrenals and the gonads

11. Pineal Gland Synthesizes Melatonin – secretes it directly into the cerebrospinal fluid – Melatonin affects rhythmic activities Circadian Rhythms – Day/Night cycles

12. Pituitary Gland

13. Hypersecretion of hGH Hyposecretion of hGH

14. Prolactin Stimulates and Maintains Milk Production in the Female Breast

15. Follicle Stimulating Hormone ~ FSH Luteinzing Hormone ~ LH Gonadotropic Hormones – FSH Follicle development in Ovaries Produce Estrogen and Eggs in Ovulation Sperm production in the Testes – LH Triggers release of Eggs from the ovary Stimulates progesterone activity Stimulates Testosterone production in males

19. Anti-Diuretic Hormone Diuresis = Urine Production ADH inhibits urine production – Increases water re-absorption – Urine volume decreases Alcohol, Diet Sodas inhibit ADH production – Increase Urine production – Water “flushed” from the body – Dehydration

20. Oxytocin Only Found during childbirth and nursing women Stimulates Birth Contractions Stimulates “Let-Down” reflex during breast feeding

21. Produces Thyroxine & Calcitonin hormones. These hormones contain iodine. Thyroxine is responsible for body’s metabolism; controls the rate at which glucose is burned for body’s energy Calcitonin decreases blood calcium levels by ushering calcium into bones ~ Deficient in the elderly leading to osteoperosis Deficiency due to lack of iodine can cause goiters (Enlarged Thyroid) and cretinism

22. Parathyroid Glands Regulate calcium homeostasis in blood When calcium levels low –Body releases PTH –PTH stimulates osteoclasts to break down bone matrix to release calcium

23. Releases hormone Releases hormone Thymosin Thymosin “programs” T-cells Large in Infants and degenerates into adulthood

24. Adrenal Gland Adrenal Cortex “Sex Hormones” ~ androgens and estrogens, ~ Secreted in minimal amounts in both sexes by the adrenal cortex, but their effect is usually masked by the hormones from the testes and ovaries. In females, the masculinization effect of androgen secretion may become evident after menopause, when estrogen levels from the ovaries decrease. Adrenal Medulla ~ Epinephrine and Norepinephrine. ~ Epinephrine is a short term “alarm” stress hormone which aids in the “fight or flight” responsiveness; increases blood glucose levels and metabolism, dilates blood vessels and airways Mineralcortoids ~ Aldosterone (Salt Levels) Glucocortoids ~ Cortisol (Long-term Stress inhibitor) Sex Hormones ~ Androgens (Male) & Estrogens (Female)

25. Secretes Glucagons and Insulin Glucagons secreted in response to a low concentration of glucose in the blood. Antagonist of Insulin Insulin aids cells for glucose intake Responds to a high concentration of glucose in the blood

26. Testes These organs are responsible for producing the sperm and ova, but they also secrete hormones and are considered to be endocrine glands. Male sex hormones are called androgens. The principal androgen is testosterone, Production of testosterone begins during fetal development, continues for a short time after birth, nearly ceases during childhood, and then resumes at puberty Function of Testosterone: ~ The growth and development of the male reproductive structures ~ Increased skeletal and muscular growth ~ Enlargement of the larynx accompanied by voice changes ~ Growth and distribution of body hair ~ Increased male sexual drive

27. Ovaries Estrogens and Progesterone. ~ These steroid hormones contribute to the development and function of the female reproductive organs, sex characteristics and changes that occur in the uterus during the female menstrual cycle At the onset of puberty Estrogens promotes: The development of the breasts Distribution of fat evidenced in the hips, legs, and breast Maturation of reproductive organs such as the uterus and vagina Progesterone causes the uterine lining to thicken in preparation for pregnancy. Together, progesterone and estrogens are responsible for the changes that occur in the uterus during the female menstrual cycle

28. Signal Transduction Pathways

29. Reception 1 EXTRACELLULAR FLUID Receptor Signaling molecule Plasma membrane CYTOPLASM 1 Signal Transduction Pathway

30. Fig. 11-6-2 Reception 1 EXTRACELLULAR FLUID Receptor Signaling molecule Plasma membrane CYTOPLASM 1 Relay molecules in a signal transduction pathway Transduction 2 Signal Transduction Pathway

31. Fig. 11-6-3 EXTRACELLULAR FLUID Plasma membrane CYTOPLASM Receptor Signaling molecule Relay molecules in a signal transduction pathway Activation of cellular response Reception TransductionResponse 1 2 3 Signal Transduction Pathway

32. Signal Reception

33. G-Protein-Linked Receptor Tyrosine Kinase Ion Channel Proteins

34. G protein-coupled receptor Plasma membrane Enzyme G protein (inactive) GDP CYTOPLASM Activated enzyme GTP Cellular response GDP P i Activated receptor GDP GTP Signaling molecule Inactive enzyme 1 2 3 4 G-Protein-Linked G-Proteins

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

36. Fig. 11-7d Signaling molecule (ligand) Gate closed Ions Ligand-gated ion channel receptor Plasma membrane Gate open Cellular response Gate closed 3 2 1 Ion Channel Proteins

37. Synapses

40. Transduction 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

41. Transduction Pathways The molecules that relay a signal from receptor to response are mostly proteins Like falling dominoes, the receptor activates another protein, which activates another, and so on, until the protein producing the response is activated At each step, the signal is transduced into a different form, usually a shape change in a protein

43. Secondary Messengers: Small Ions/Molecules Second messengers are small, non-protein, 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

44. Adenylyl cyclase Pyrophosphate P P i ATP cAMP Phosphodiesterase AMP Cyclic AMP (cAMP) vs. Adenylyl cyclase

45. First messenger G protein Adenylyl cyclase GTP ATP cAMP Second messenger Protein kinase A G protein-coupled receptor Cellular responses

46. Role of Calcium 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 (IP 3 ) and diacylglycerol (DAG) as additional second messengers

47. Fig. 11-13-1 EXTRA- CELLULAR FLUID Signaling molecule (first messenger) G protein GTP G protein-coupled receptor Phospholipase C PIP 2 IP 3 DAG (second messenger) IP 3 -gated calcium channel Endoplasmic reticulum (ER) Ca 2+ CYTOSOL

48. Fig. 11-13-2 G protein EXTRA- CELLULAR FLUID Signaling molecule (first messenger) G protein-coupled receptor Phospholipase C PIP 2 DAG IP 3 (second messenger) IP 3 -gated calcium channel Endoplasmic reticulum (ER) Ca 2+ CYTOSOL Ca 2+ (second messenger) GTP

49. Fig. 11-13-3 G protein EXTRA- CELLULAR FLUID Signaling molecule (first messenger) G protein-coupled receptor Phospholipase C PIP 2 DAG IP 3 (second messenger) IP 3 -gated calcium channel Endoplasmic reticulum (ER) Ca 2+ CYTOSOL Various proteins activated Cellular responses Ca 2+ (second messenger) GTP

51. Responses Ultimately, a signal transduction pathway leads to regulation of one or more cellular activities – The response may occur in the cytoplasm or may involve action in the nucleus – Many signaling pathways regulate the synthesis of enzymes or other proteins, usually by turning genes on or off in the nucleus – The final activated molecule may function as a transcription factor What other changes do these responses elicit?

53. Fine Tuning Response Multistep pathways have two important benefits: – Amplifying the signal (and thus the response) Enzyme cascades amplify the cell’s response At each step, the number of activated products is much greater than in the preceding step – Contributing to the specificity of the response Different Proteins = Different Signals in different cells

54. Termination of Signal Inactivation mechanisms are an essential aspect of cell signaling When signal molecules leave the receptor, the receptor reverts to its inactive state