cell biology 16 - intercellular signaling
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Cell Biology 16 - Intercellular signaling. Sung Youn Lee, PhD. Student Veterinary collage, Room 320 02 450 3719, 016 293 6059 [email protected]. Cell Signaling. Cell communication : why? Multicellular organism Cell communication : how? A variety messengers - PowerPoint PPT PresentationTRANSCRIPT
Cell Biology 16Cell Biology 16- Intercellular signaling- Intercellular signalingCell Biology 16Cell Biology 16- Intercellular signaling- Intercellular signaling
Sung Youn Lee, PhD. StudentSung Youn Lee, PhD. StudentVeterinary collage, Room 320Veterinary collage, Room 32002 450 3719, 016 293 605902 450 3719, 016 293 6059
[email protected]@paran.com
Cell Signaling• Cell communication : why?
– Multicellular organism• Cell communication : how?
– A variety messengers– Endocrine(hormone), Paracrine, Neurotrans
mitter, Autocrine
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, p
eptide and catecholamine (epinephrine and norepinephrine),
– Cytoplasm (steroid)– Nucleus (thyroxine)
Hormonal secretion• Regulated exocytosis – special secretor
y vesicle• Ligand and surface receptor binding• Ca2+ rising --> triger the fusion of vesicl
e and plasma membrane
Steroid hormone• Similar to that of cholesterol
– Adrenal cortex : cortisol & aldosterone– Ovaries : estrogen & progesterone– Testes : testosterone(androgen)– Placenta : estrogen & progesterone
Neurosecretory cell• Resemble both endocrine cells and neuro
ns (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 stim
ulate the release of a secondary hormones.
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 (smoot
h muscle contraction)• Angiotensin II - thirst• Cholecystokinin - eating
Neurosecretory cell• Pituitary a.
• Growth hormone• ACTH (adrenocorticotropic hormone)• Thyroid-stimulating hormone• Follicle-stimulating hormone• Luteinizing hormone• Prolactin
Drawings by Leonardo da Vinci (1508-1509)
(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).
Adrenal cortex : corticoid (mineralocorticoid and glucocorticoid)Adrenal medulla : catecholamines (epinephrine and norepinephrine)
Zona glomerulosa -aldosterone (mineralocorticoid)
Zona fasiculata and reticularis - cortisol and cortisone (glucotorticoid)
Paracrine communication• Do not enter the circulation• Highly localized
Growth factors• Soluble polypeptides• All cells make polypeptide growth factors• Function : mitogen, trophic factors, chemoattractan
ts• 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)
Growth factors
Activates a different signal transduction pathways
Pleotropic response in a single cell
Switch mitogen to trophic stimulus
Blast stage Mature
Nerve growth factor• Require for survival and differentiation• 50% neurons < die normally (excess innervati
on to target ; why? - Assured)• Nerve growth factors (NGF)
– chemoattractant molecules– Homodimer – two 118 a.a. chains coupled by disu
lfied bond
50%< die
Nerve growth factor• NGF binds to NGF receptors on the growth c
ones of approaching axons.• It is internalized by receptor mediated endocyt
osis 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)
팀 동료인 베이브 루스와 함께 1 루수를 맡으며 메이저리그 역사상 가장 견고한 1, 2 번을 구축했다는 평을 받는다 . 한 시즌 100 득점 이상을 13 시즌 연속으로 수립하였고 , 150 타점 이상을 7 번이나 기록하였으며 , 1932 년에는 한경기에 4연속 홈런을 때려 20 세기 들어 첫번째 선수가 되는 영광도 누렸다 .역대 타점 랭킹 1, 2 위 선수들이 21-23 시즌에 2200 타점을 넘어섰지만 루 게릭은 단 14 시즌동안 1995 타점을 기록하였다 . 이 외에 12 년 연속 3 할 타율 , 13 년 연속 100 타점 -100 득점 , 최다 400 총루타 5 회 , 사이클링 히트 2 회도 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 .
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 targ
et cell (muscle cell)– --> motor neuron ▽--> muscle▽
No NGF
50 ng/ml NGF
Nerve growth factor• Programmed cell death : how?
– Can prevent PCD with protein and mRNA systhesis inhibitor
– Ex, cycloheximide and actinomycin D– ==> autolytic enzyme
Extracellular matrix• Growth factors
– Most of them are soluble peptides, not all
– There is growth factors that attached to cell membrane or matrix
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
Autocrine• PDGF : cytotrophoblast – placenta• IL-2 : T helper cell• These are mitogen.
PDGF
Histamine• Mast cell reside in the connective tissu
e throughout the body.• They have IgE receptor and histamine in
their secretory vesicle.
Ecosanoids• Ecosanoid ; 20-carbon polyunsaturated fatty
acids (prostaglandins, thromboxanes, leukotrienes, and other active metabolites)
• Highly diffusible through membrane.• Biological effects of PGs
– Smooth muscle contraction / platelet aggregation / uterine contraction / cause inflammation (nociceptor-pain)
– Aspirin, indomethacin and NSAID
Asprin, Ibupropen, Indomethacin
steroid
NO nitric oxide• Highly diffusible through membrane.• Biological effects of NO
– Memory in brain– Relaxation of blood vessel
• Mechanism of vasodilation– Endothelial cell contain NO synthase (Fig 7-16)– Ach binds muscarinic receptor on the surface of endothelial cell– G protein mediated signal transduction– Ca2+ increase– NO synthase
– Nitroglycerin is rapidly converted to NO in the blood
Synaptic transmission
Ach
EpinehprineNorepinephrine
Ach Ach
Symphathetic
Parasymphathetic
Ach
Ach Ach-muscarinic-nicotinic
EpinehprineNorepinephrineAch : sweat glands and vasodilation (skeletal muscle)
Muscarinic Acetylcholine Receptors
M1 M2 M3 M4 M5
Distribution
Cerebral cortex,
hippocampus
HeartExocrine
glands, GI tract
Neostriatum Substantia nigra
Antagonists
Pirenzepine AF-DX 116 pF-HHSiD
AgonistsXanomeline, CDD-0097
G protein Gq/11 Gi/o Gq/11 Gi/o Gq/11
Intracellular response
Phospholipase C
Adenylyl cyclase inhibitio
n
Phospholipase C
Adenylyl cyclase inhibitio
n
Phospholipase C
Nicotinic Acetylcholine Receptors
ReceptorSkeletal muscle
Autonomic ganglion
CNS CNS
Subunits 1,1,,() 3,5,7,2,4
3,4,2,4 7,8,9
-Bungarotoxin + +/- - +
Antagonists -Bungarotoxin Hexamethonium
Dihydro--erythroidine -Bungarotoxin
Mecamylamine Mecamylamine
Agonists Epibatidine Epibatidine
Epibatidine
ABT-418
Two forms of synapse
Speed : heart and gut
1 msec delay
Chemical neurotransmitter
• Fast-acting neurotransmitters– Acetylcholine– GABA(γ-amino butyric acid)– Glycine– Glutamate
• Slow-acting neurotransmitters– Catecholamine (dopamine, norepi, epi)– Indoleamine (serotonin, histamine)– Various neuropeptides
Directly open the channel
Indirectly open the channel
Different messengers localized to different
types of vesicle in nerve terminals
Vesicle Small LargeSize 50nm 90-250nmShape lucent denseVelocity Fast a. Slow a.
The skeletal neurouscular junction
Synaptic vesicle• ~ 5,000 molecules/vesicle• MEP miniature synaptic potential --
> single synaptic vesicle release• 1mV• With Ca2+
Multiple synaptic inputs converge on a single
neuron• Na+/Cl-• Excitatory/Inhibitory• Integration• EPSP excitatory p s p• IPSP inhibitory p s p
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