Cell Signalling Flashcards

1
Q

biological role of signal transduction

A

Cells receive signals from the environment beyond the plasma membrane. Types of signals include: antigens, hormones, neurotransmitters, light, touch, pheromones

These signals cause changes in the cell’s composition and function, such as: differentiation and antibody production, growth in size or strength, cell division (proliferation), migration

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2
Q

receptors function

A
  • interact with signals and translate message to cell
  • Receptor: A membrane-bound or soluble protein or protein complex, which exerts a physiological effect after binding its natural ligand
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3
Q

typical ligands

A

Small ions - ferric ion: bacterial ferric receptor

Organic molecules - adrenalin: epinephrine receptor

Polysaccharides - heparin: fibroblast growth factor or ATIII

Peptides - insulin: insulin receptor

Proteins - vascular endothelial growth factor: VEGF receptor

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4
Q

six features of signal-transducing systems

A

a. Specificity
b. Amplification
c. Modularity
d. De-sensitization/Adaptation
e. Integration
f. Localized Response

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5
Q

receptors bind specific ligands

A

signal molecule fits binding site on its complementary receptor; other signals do not fit
Kd = dissociation constant – low Kd – high affinity

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6
Q

types of receptors (4 main)

A
  1. G protein−coupled receptors - epinephrine receptor
  2. Enzyme-linked receptors - insulin receptor
  3. Ligand-gated ion channels - nicotinic acetylcholine receptor
  4. Nuclear receptors - steroid receptors
  5. Other membrane receptors – integrin receptors
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7
Q

G protein-coupled signalling (GPC)

A

GPCRs are α-helical integral membrane proteins

  • G proteins are membrane associated proteins that bind GTP
  • G proteins mediate signal transduction FROM GPCRs TO other target proteins

example: Ras - oncogene protein, and adrenaline - interacts with cells via a GPCR
- stress response, mobilises E, induces liver cells to breakdown glycogen to release glucose

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8
Q

synthesis of cAMP

A

cAMP is a secondary messenger

  • allosterically activates a variety of enzymes including cAMP-dependent protein kinase A (PKA)
  • PKA activation leads to activation of enzymes that release glucose from glycogen
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9
Q

signal amplification cascade

A

eg in adrenaline

  • activation of a few GPCRs leads to the activation of enzymes
  • every enzyme makes several cAMP molecules
  • therefore several PKA enzymes
  • activates 1000s of glycogen degrading enzymes in liver
  • therefore abundance of glucose released into bloodstream
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10
Q

desensitisation/adaptation

A

receptor activation triggers a feedback circuit that shuts off the receptor or removes it from cell surface.
eg down regulation of cAMP via hydrolysis of GTP in α subunit of G-protein

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11
Q

enzyme linked membrane receptors

A

consist of extracellular ligand-binding domain and intracellular catalytic domain
- most common catalytic domain has tyrosine kinase activity (adds phosphate group to itself, leads to conformational change allowing binding and catalytic phosphorylation of specific target proteins)

  • eg insulin acts via a receptor tyrosine kinase
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12
Q

integration

A

when 2 signals have opposite effects on a metabolic characteristic - such as concentration of a second messenger - the regulatory outcome results from the integrated input from both receptors

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13
Q

modularity

A

proteins with multivalent affinities form diverse signalling complexes from interchangeable parts. phosphorylation provides reversible points of interaction

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14
Q

ligand-gated ion channels

A

regulates transport of ions across cell membranes

  • respond to changes in membrane potential and ligand binding to specific receptor sites
  • roles in NS inc: voltage-gated Na channels, nicotinic acetylcholine receptor, ionotropic glutamate receptor, gamma aminobutyric acid receptor A
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15
Q

membrane electrically polarised

A

inside of cell is negative charged compared with outside (~-50 to -70mV difference)

  • membrane potential largely d/t asymmetric transport of Na+ and K+ via ATPase (for every 3 Na+ out, only 2 K+ in)
  • flow of ionic species across the membrane depends on concentration gradient and overall electrical potential
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16
Q

example of voltage gated and ligand gated ion channels in nerve signalling

A
  • nerve signals within nerve propagate as electrical impulses
  • propagation of impulse involves opening of voltage-gated Na+ channels
  • opening of voltage gated Ca2+ channels at end of axon triggers release of neurotransmitter acetylcholine
  • acetylcholine opens the ligand-gated ion channel on the receiving cell
17
Q

PROCESS example of voltage gated and ligand gated ion channels in nerve signalling

A
  1. depolarisation (Na+ channel open and Na+ flows in)
  2. repolarisation (K+ channel open and K+ flows out)
  3. voltage gated Ca2+ open triggering secretory versicles containing acetylcholine released
  4. acetylcholine crosses synaptic cleft to other cell, and
  5. binds to receptor ion channels on the cell
  6. Na and Ca flow into new cell causing action potential to propagate again
18
Q

nuclear receptors

A

direct regulation of transcription by hormones

  1. hormone carried to target tissue on serum binding protein - diffuse across PM
  2. hormone bind to receptor in nucleus –> conformational change on receptor. forms diner with other hormone/receptor complexes. bind to hormones response elements on DNA
  3. hormone receptor complex attract other activators or repressors. lead to inc or dec in mRNA transcription
  4. altered levels of gene product translated –> cellular response
19
Q

interns mediate cell adhesion

A
  • extracellular domain interacts with AA containing ECM proteins - collagen, fibrinogen etc
  • triggers cytoskeleton rearrangement and gene expression
  • newly expressed genes bind to intracellular domain, triggering extracellular response –> proliferation and migration