Cell Biology 16 - Intercellular signaling

1. Cell Biology 16- Intercellular signaling Sung Youn Lee, PhD. Student Veterinary collage, Room 320 02 450 3719, 016 293 6059 leevet@paran.com

2. Cell Signaling • Cell communication : why? • Multicellular organism • Cell communication : how? • A variety messengers • Endocrine(hormone), Paracrine, Neurotransmitter, Autocrine

4. Hormones and Endocrine signaling • Classification by nature • Steroid, protein, amino acids • Classification by initial action • The location of receptor • Cell surface (in the membrane) ; protein, peptide and catecholamine (epinephrine and norepinephrine), • Cytoplasm (steroid) • Nucleus (thyroxine)

5. Hormonal secretion • Regulated exocytosis – special secretory vesicle • Ligand and surface receptor binding • Ca2+ rising --> triger the fusion of vesicle and plasma membrane

11. Steroid hormone • Similar to that of cholesterol • Adrenal cortex : cortisol & aldosterone • Ovaries : estrogen & progesterone • Testes : testosterone(androgen) • Placenta : estrogen & progesterone

13. Neurosecretory cell • Resemble both endocrine cells and neurons (dual properties) • Hypothalamus • TRH (thyrotropin releasing hormone) • GnRH (gonadotropin releasing hormone) • CRH (corticotropin releasing hormone) • GRH (growth hormone releasing hormone) • These reach the pituitary and supress or stimulate the release of a secondary hormones.

15. Neurosecretory cell • Hypothalamus • Peptidergic (peptide-secreting) neuroendocrine cells extend axons into the posterior pituitary • Pituitary p. • Vasopressin - BP△ (by vasoconstriction and water resorption by kidney) • Oxytocin – uterus contraction and lactation (smooth muscle contraction) • Angiotensin II - thirst • Cholecystokinin - eating

16. Neurosecretory cell • Pituitary a. • Growth hormone • ACTH (adrenocorticotropic hormone) • Thyroid-stimulating hormone • Follicle-stimulating hormone • Luteinizing hormone • Prolactin

19. Drawings by Leonardo da Vinci (1508-1509)

20. (A) Detail from the fresco, "Creation of Adam," by Michelangelo Buonarroti, 1508-1512 (B) The contour of the same image is reminiscent of a midline saggital section of the brain and includes the hypothalamus, pituitary and brainstem. (From Toni R., The human hypothalamus: clinical anatomy of endocrine, autonomic and behavioral responses, J. Endocrinol. Invest 2003, in press).

25. Adrenal cortex : corticoid (mineralocorticoid and glucocorticoid) Adrenal medulla : catecholamines (epinephrine and norepinephrine)

26. Zona glomerulosa -aldosterone (mineralocorticoid) Zona fasiculata and reticularis - cortisol and cortisone (glucotorticoid)

32. Paracrine communication • Do not enter the circulation • Highly localized

33. Growth factors • Soluble polypeptides • All cells make polypeptide growth factors • Function : mitogen, trophic factors, chemoattractants • 10-30 kDa, more than 100 (Table 7-2) • Ex, PDGF platelet-dervied growth factor • Mitogen and trophic factors ; fibroblast & smooth muscle cells • Chemoattractants ; fibrolasts & macrophages (blood clotting)

34. Growth factors Activates a different signal transduction pathways Switch mitogen to trophic stimulus Pleotropic response in a single cell Blast stage Mature

37. Nerve growth factor • Require for survival and differentiation • 50% neurons < die normally (excess innervation to target ; why? - Assured) • Nerve growth factors (NGF) • chemoattractant molecules • Homodimer – two 118 a.a. chains coupled by disulfied bond

38. 50%< die

41. Nerve growth factor • NGF binds to NGF receptors on the growth cones of approaching axons. • It is internalized by receptor mediated endocytosis and transported retrogradely to the cell body, where it undergoes lysosomal degradation. • NGF supports the survival of cholinergic nerons. • Alzheimer disease (cholinergic neuron for memory)

43. 팀 동료인 베이브 루스와 함께 1루수를 맡으며 메이저리그 역사상 가장 견고한 1, 2번을 구축했다는 평을 받는다. 한 시즌 100득점 이상을 13시즌 연속으로 수립하였고, 150타점 이상을 7번이나 기록하였으며, 1932년에는 한경기에 4연속 홈런을 때려 20세기 들어 첫번째 선수가 되는 영광도 누렸다.역대 타점 랭킹 1, 2위 선수들이 21-23시즌에 2200타점을 넘어섰지만 루 게릭은 단 14시즌동안 1995타점을 기록하였다. 이 외에 12년 연속 3할 타율, 13년 연속 100타점-100득점, 최다 400 총루타 5회, 사이클링 히트 2회도 그의 이름을 드높이는 결과이다.근위축성 측색 경화증(ALS)이란 희귀병에 걸려 사망하였는데, 이후 이 병은 그의 이름을 따 '루 게릭병'으로 명명되어 그의 아까운 죽음을 기리고 있다.

44. Nerve growth factor • Lou Gehrig’s disease • = ALS (amyotrophic lateral sclerosis) • CNTF (ciliary neurotrophic factor) • PNS : schwann cell • CNS : astrocyte • Cf. other neurotrophic factors are secreted by target cell (muscle cell) • --> motor neuron ▽--> muscle▽

45. No NGF 50 ng/ml NGF

46. Nerve growth factor • Programmed cell death : how? • Can prevent PCD with protein and mRNA systhesis inhibitor • Ex, cycloheximide and actinomycin D • ==> autolytic enzyme

48. Extracellular matrix • Growth factors • Most of them are soluble peptides, not all • There is growth factors that attached to cell membrane or matrix

49. 1) Low affinity receptors bind to -free heparin -heparan sulfate chain 2) Comformational change by proteoglycan 3) High affinity receptors 4) Prolongs the resistance of HBGF 5) Regeneration and/or carcinogenesis

50. Autocrine • PDGF : cytotrophoblast – placenta • IL-2 : T helper cell • These are mitogen.