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
• leevet_at_paran.com

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Cell Signaling

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

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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)

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Hormonal secretion

• Regulated exocytosis special secretory vesicle
• Ligand and surface receptor binding
• Ca2 rising --gt triger the fusion of vesicle and
  plasma membrane

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Steroid hormone

• Similar to that of cholesterol
• Adrenal cortex cortisol aldosterone
• Ovaries estrogen progesterone
• Testes testosterone(androgen)
• Placenta estrogen progesterone

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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.

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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

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Neurosecretory cell

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

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Drawings by Leonardo da Vinci (1508-1509)
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(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).
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Adrenal cortex corticoid (mineralocorticoid and
glucocorticoid) Adrenal medulla catecholamines
(epinephrine and norepinephrine)
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Zona glomerulosa -aldosterone
(mineralocorticoid) Zona fasiculata and
reticularis - cortisol and cortisone
(glucotorticoid)
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Paracrine communication

• Do not enter the circulation
• Highly localized

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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)

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

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

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50lt die
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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)

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Nerve growth factor

• Lou Gehrigs 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)
• --gt motor neuron ?--gt muscle?

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No NGF
50 ng/ml NGF
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Nerve growth factor

• Programmed cell death how?
• Can prevent PCD with protein and mRNA systhesis
  inhibitor
• Ex, cycloheximide and actinomycin D
• gt autolytic enzyme

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Extracellular matrix

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

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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
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Autocrine

• PDGF cytotrophoblast placenta
• IL-2 T helper cell
• These are mitogen.

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PDGF
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Histamine

• Mast cell reside in the connective tissue
  throughout the body.
• They have IgE receptor and histamine in their
  secretory vesicle.

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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

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steroid
Asprin, Ibupropen, Indomethacin
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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

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Synaptic transmission
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Ach
Epinehprine Norepinephrine
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Ach
Ach
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Symphathetic
Epinehprine Norepinephrine Ach sweat glands
and vasodilation (skeletal muscle)
Ach
Parasymphathetic
Ach
Ach -muscarinic -nicotinic
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Muscarinic Acetylcholine Receptors Muscarinic Acetylcholine Receptors Muscarinic Acetylcholine Receptors Muscarinic Acetylcholine Receptors Muscarinic Acetylcholine Receptors Muscarinic Acetylcholine Receptors
M1 M2 M3 M4 M5
Distribution Cerebral cortex, hippocampus Heart Exocrine glands, GI tract Neostriatum Substantia nigra
Antagonists Pirenzepine AF-DX 116 pF-HHSiD
Agonists Xanomeline, CDD-0097
G protein Gaq/11 Gai/o Gaq/11 Gai/o Gaq/11
Intracellular response Phospholipase Cb Adenylyl cyclase inhibition Phospholipase Cb Adenylyl cyclase inhibition Phospholipase Cb
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Nicotinic Acetylcholine Receptors Nicotinic Acetylcholine Receptors Nicotinic Acetylcholine Receptors Nicotinic Acetylcholine Receptors Nicotinic Acetylcholine Receptors
Receptor Skeletal muscle Autonomic ganglion CNS CNS
Subunits a1,b1,d,g(e) a3,a5,a7,b2,b4 a3,a4,b2,b4 a7,a8,a9
a-Bungarotoxin /- -
Antagonists a-Bungarotoxin Hexamethonium Dihydro-b-erythroidine a-Bungarotoxin
Antagonists a-Bungarotoxin Hexamethonium Mecamylamine Mecamylamine
Agonists Epibatidine Epibatidine Epibatidine
Agonists Epibatidine Epibatidine ABT-418
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Two forms of synapse
1 msec delay
Speed heart and gut
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Chemical neurotransmitter

• Fast-acting neurotransmitters
• Acetylcholine
• GABA(?-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
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Different messengers localized to different types
of vesicle in nerve terminals

• Vesicle Small Large
• Size 50nm 90-250nm
• Shape lucent dense
• Velocity Fast a. Slow a.

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The skeletal neurouscular junction
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Synaptic vesicle

• 5,000 molecules/vesicle
• MEP miniature synaptic potential --gt single
  synaptic vesicle release
• 1mV
• With Ca2

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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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Thank you for your attention