2.9 - Cell Signalling Flashcards

1
Q

Why do cells need to communicate?

A
  1. to process information (sensory stimuli e.g. light and sound)
  2. self-preservation (identify danger and take appropriate actions e.g. spinal reflexes and sympathetic NS) - innate
  3. voluntary movement
  4. homeostasis (e.g. thermoregulation, BGC)
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2
Q

Endocrine signalling

A

Hormone travels within blood vessels to act on a distant target cell

  • e.g. glucagon is secreted by alpha cells of Islets of Langerhans and travels out of pancreas in blood vessels, stimulating gluconeogenesis and glycogenolysis within the liver = increased BGC
  • e.g. insulin produced in the pancreas acts on the liver, muscle cells and adipose tissue
  • e.g. adrenaline produced in the adrenal glands acting on the trachea
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3
Q

Paracrine signalling

A

Hormone acts on an adjacent cell

  • e.g. insulin produced by beta cells in response to hyperglycaemia acts on alpha cells to inhibit glucagon secretion
  • e.g. nitric oxide produced by endothelial cells in blood vessels, acts on smooth muscle cells = vasodilation
  • e.g. osteoclast activating factors produced by adjacent osteoblasts
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4
Q

Signalling between membrane-attached proteins

A

Plasma membrane proteins on adjacent cells interacting

  • e.g. TCR interacting with MHC class II molecule - blood borne virus detected within bloodstream by APC, which digests pathogen = expresses MHC class II molecules on surface, circulating T cell engages with MHC through TCR interaction
  • e.g. HIV GP120 glycoprotein interacts with CD4 receptor on T cells
  • e.g. bacterial cell wall components binding to toll-like receptors on haematopoietic stem cells
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5
Q

Autocrine signalling

A

Signalling molecule acts on same cell

  • involved in positive or negative feedback
  • e.g. interleukin-2 acting on T lymphocytes - activated T cell expresses interleukin-2 which binds to IL-2 receptor on same cell
  • e.g. acetylcholine acting on presynaptic M2 muscarinic receptors
  • e.g. growth factors (e.g. TGFB) from tumour cells leading to mitogenesis
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6
Q

Neurotransmission (intracellular signalling)

A
  1. Propagation of action potential
    - AP propagated by VGSCs opening
    - Na+ influx –> membrane depolarisation –> AP ‘moves along’ neurone
    - VGKC opening –> K+ efflux –> repolarisation
  2. NT release from vesicles
    - AP opens voltage-gated Ca2+ channels at presynaptic terminal
    - Ca2+ influx –> vesicle exocytosis
  3. Activation of postsynaptic receptors
    - NT binds to receptors on postsynaptic membrane
    - receptors modulate postsynaptic activity
    - the signal can be transmitted by a variety of different types of receptor
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7
Q

Ionotropic receptor

A
  1. ligand (molecule which binds to receptor) binds to receptor protein
  2. change in conformation of channel protein –> opening of pore
  3. pore allows ions to move in and out of cell according to their respective concentration gradients
  • e.g. nicotinic acetylcholine
  • ligand - acetylcholine
  • location - skeletal muscle
  • physiological effect - muscle contraction
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8
Q

G-protein coupled receptor

A
  • ligand binding –> activates intracellular G protein
    1. in resting state the G protein complex consists of a Ga subunit, GBy subunit and an associated GDP molecule, which are in close proximity to the receptor. 7-transmembrane receptor and heterotrimeric G-protein are inactive
    2. ligand binding –> changes conformation of receptor
    3. unassociated G-protein binds to the receptor –> GDP is exchanged for GTP (allows heterotrimer to dissociate)
    4. G-protein dissociates into two active components: a-subunit and By subunit (GTP stays attached to alpha component). They bind to their target proteins and both can act as second messengers
    5. internal GTPase activity on a-subunit dephosphorylates GTP –> GDP
    6. a-subunit dissociates from target protein –> inactive again = heterotrimer reformed as Ga and GBy reassociate
    7. receptor remains active as long as ligand is bound and can activate further heterotrimeric G-proteins
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9
Q

Examples of G-protein coupled receptors

A
  1. Gs protein linked receptor - stimulates adenylyl cyclase
    - converts ATP to cAMP, which activates protein kinase A (PKA)
    - e.g. B1-adrenergic receptor (fight / flight)
  2. Gi protein linked receptor - inhibits adenylyl cyclase
    - reduces levels of PKA
    - e.g. M2-muscarinic receptor (rest / digest)
  3. Gq protein linked receptor - stimulates phospholipase C (PLC)
    - converts PIP2 –> IP3 + DAG
    - IP3 stimulates CA2+ release
    - DAG activates PKC
    - e.g. AT-1 angiotensin receptor
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10
Q

Enzyme-linked receptor

A
  1. ligand binding –> receptor clustering
  2. activates internal enzyme activity within cytoplasmic domain
  3. enzymes phosphorylate receptor
  4. phosphorylation –> binding of signalling proteins to cytoplasmic domain
  5. these signalling proteins –> recruit other signalling proteins –> signal is generated –> cascade
  • e.g. insulin receptor (CD220 antigen): ligand - insulin; physiological effect - glucose uptake
  • e.g. ErbB receptors: ligand - epidermal growth factor, transforming growth factor B; physiological effect - cell growth and proliferation
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11
Q

Intracellular receptor - Type 1

A
  • a membrane permeable ligand binds to receptor inside cell
    Type 1 - cytoplasmic
    1. located within cytosolic compartment
    2. associated with chaperone molecules (heat shock proteins / HSP)
    3. hormone binds to receptor –> HSP dissociates
    4. two hormone bound receptors form a homodimer
    5. the homodimer translocates to the nucleus –> binds to DNA
  • e.g. glucocorticoid receptor
  • ligands: cortisol, corticosterone
  • physiological effect: reduced immune response, increased gluconeogenesis
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12
Q

Intracellular receptor - Type 2

A

Type 2 - nuclear
1. located within the nucleus
2. binding of hormone ligand (directly to nucleus) –> transcriptional regulation

  • e.g. thyroid hormone receptor
  • ligand: thyroxine (T4), triiodothyronine (T3)
  • physiological effect: growth and development
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