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Concepts of cell signalling (4 different types of cell signalling…
Concepts of cell signalling
What is cell signalling?
usually involves a receptor molecule that recognises the signal in a highly specific manner
allows the recieving cell to make a characteristic response
Why is cell signalling important?
essential for co-ordination of cell behaviour
multicellular organisms depend on cell signalling for correct development, tissue maintenance and homeostasis
3 key concepts of cell signalling
cells may respond to a range of signals
changes in cell behaviour may result from the integration of many signals
examples
signals A, B and C cause the cell to survive
signals A, B, C, D, E cause cell to grow and divide
signals A B C D F G --> cell differentiates
no signal --> cell dies
response to signals is cell-type specific
same signal brings about different resoonse in different cells
example of acetylcholine
heart pacemaker cell
decreased rate of firing
salivary gland cell
secretion
skeletal muscle cell
contraction
each type of signal has a specific receptor
cell surface receptors
G-protein coupled receptors
receptor tyrosine kinases
intracellular receptors
guanyl cyclase activated by NO
4 different types of cell signalling
endocrine signalling
hormones
example:
signal molecule
insulin
site of origin
b cells of pancreas
some actions
stimulates glucose uptake
protein synthesis
lipid synthesis in various cells
paracrine signalling
local mediators
example
signal molecule
Nitric Oxide (NO)
site of origin
nerve cells
endothelial cells lining blood vessels
some actions
smooth muscle cells to relax
regulates nerve-cell activity
neuronal signalling stimulates production of NO in endothelial cells that act as a signal in smooth muscle cells
dilates blood vessel = increased blood flow
viagra treatment
cGMP increase causes blood dilation
can be stopped by conversion of cGMP to 5-GMP by cGMP phosphodiesterase
viagra inhibits action of phosphodiesterase
NO synthase activated by nerve terminal
rapid diffusion of NO across membranes
NO bound to guanlyl cyclase
GTP hydrolysis to cyclic AMP
rapid relaxation of smooth muscle cell
synaptic signalling
neurotransmitters
example
signal molecule
acetylcholine
site of origin
nerve terminals
some actions
excitatory at many nerve muscle synapses
excitatory in the central nervous system
acetylcholine and smoking
normal conditions
acetylcholine binding to nicotinic receptor
conformational change in the receptor
lets Na+ in
desensitisation before going back to original conformation
nicotine can bind to receptor
continuous exposure to nicotine overstimulates receptor
receptor remains desensitised for longer --> prevented from returning to its original conformation
contact dependent signalling
membrane bound
example:
signal molecule
delta
site of origin
prospective neurons
other developing cell types
some actions
inhibits neighbouring cells from becoming specialised in the same way as the signalling cell
lateral inhibition mediated by the delta notch signalling system
tissue development
nervous system
specialised cell types
neurons
support cells
signal: delta
high levels of delta
inhibits neurogenin expression in neighbouring cells
reduces expression of delta in neighbouring cell
stimulates neurogenin expression in signalling cell
allows expression of factors such as Neuro D
initiates neuronal differentiation
receptor: notch
What happens after signal binding?
Signal-receptor interaction starts a chain of molecular changes within the cell
receptors are linked to different intracellular signal transduction pathways
result in changes
in the cytoplasm
altered metabolisl
altered cytoskeleton
in the nucleus
altered gene expression
of the signalling pathway
cross talk with other signalling pathways
amplification of the pathway
small hydrophobic signal molecules can interact with intracellular receptors
signals can cross the plasma membrane
interaction with intracellular receotors
directly activate DNA transcription
the hormone-receptor complex enters the nucleus and acts directly as a transcription factor
examples
steroid hormones
cortisol
testosterone
thyroid hormones
thyroxine