Second messengers

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Transcript Second messengers

Cell to Cell Communication
Chapter 11
Example of Cell to Cell Communication
• Yeast’s version of sex
• Two types of cells (a and )
• Each secretes a mating factor that binds
to receptor on opposite cell
• Binding of mating factors lead to cell
growth and fusion
• Nucleus of fused cell contains DNA
from both a and .
Figure 11.0 Yeast
Figure 11.1 Communication between mating
yeast cells
Local and Long Distance Signaling
• Local signaling – influences cells in the
nearby vicinity
– Paracrine signaling – secreting cell releases
a regulator in the the extracellular matrix
– Synaptic signaling – nerve cell releases
neurotransmitter into a synapse (space
between nerves)
• Long Distance signaling – can influence cells
all over body
– Hormone signaling – endocrine cells
secrete hormones into blood where they can
reach any cell
Figure 11.3 Local and long-distance cell
communication in animals
Figure 11.4 Communication by direct contact
between cells
Cell junctions and cell-cell recognition
Three Stages of Cell Signaling
• Reception – target cell’s detection of a
chemical signal
– Signal is detected when it binds to a
receptor
– Ligand – a signal molecule that binds to a
receptor
• Transduction – binding of signal to receptor
stimulates a change in the receptor.
– The changed receptor triggers a step or
many steps that lead to the cell response.
• Response – end result – the cell response
Figure 11.5 Overview of cell signaling (Layer 1)
Figure 11.5 Overview of cell signaling (Layer 2)
Figure 11.5 Overview of cell signaling (Layer 3)
Receptors
• Intracellular receptors – found in cytoplasm or
on nucleus so signal must pass through cell
membrane first
– Ex. NO and steroid hormones like
testosterone
– Testosterone receptor only found in certain
cells
• An activated testosterone receptor acts
as a transcription factor
– Transcription factors - turn on or turn off
genes
Figure 11.10 Steroid hormone interacting with
an intracellular receptor
• Cell Membrane Receptors – found in
cell membrane
– Three major types
• G-linked receptor
• Receptor tyrosine kinase
• Ligand-gated ion channel
Figure 11.6 The structure of a G-protein-linked
receptor
Figure 11.7 The functioning of a G-proteinlinked receptor
Figure 11.8 The structure and function of a
tyrosine-kinase receptor
Figure 11.9 A ligand-gated ion-channel
receptor
Transduction
• Signal transduction pathways – a chain of
molecular interactions (like falling dominoes)
• Often involves protein phosphorylation and
dephosphorylation
– Protein kinases – enzymes that transfer
phosphate groups from ATP to a protein
– Phosphorylation of protein often changes
protein from inactive to active form
– Protein phosphatases – enzymes that
rapidly remove P (often turn off pathway)
Figure 11.11 A phosphorylation cascade
Second Messengers
• Second messengers – small,
nonprotein, water-soluble molecules or
ions that are part of signaling pathways
• Two most common second messengers
– Ca2+
– Cyclic adenosine monophosphate
(cAMP or cyclic AMP)
cAMP
• Adenylyl cyclase – an enzyme in cell
membranes that converts ATP into
cAMP
• Phosphodiesterase – an enzyme that
converts cAMP into AMP
Figure 11.12 Cyclic AMP
Figure 11-12x cAMP
Figure 11.13 cAMP as a second messenger
Ca2+
• Second messenger involved in growth
factors, some hormones, muscle
contractions, neurotransmitters, and cell
division
• Ca2+ levels are high in the blood, ER,
and sometimes mitochondria and
chloroplasts
• Low Ca2+ cytosol concentration allows
even small fluctuations to trigger
pathways
Figure 11.14 The maintenance of calcium ion
concentrations in an animal cell
Figure 11.15 Calcium and inositol triphosphate
in signaling pathways (Layer 1)
Figure 11.15 Calcium and inositol triphosphate
in signaling pathways (Layer 2)
Figure 11.15 Calcium and inositol triphosphate
in signaling pathways (Layer 3)
Figure 11.16 Cytoplasmic response to a signal: the
stimulation of glycogen breakdown by epinephrine
Figure 11.17 Nuclear response to a signal: the
activation of a specific gene by a growth factor
Fine Tuning of Response
• Signal Amplification – number of activated
products is much greater than in preceding
step
• Specificity – different cells have different
proteins so two cells can respond to same
signal in different manner
– Ex. epinephrine stimulates liver to break
down glycogen and heart cells to contract
faster
• Scaffolding Proteins – large relay proteins
to which several other relay proteins are
attached
Figure 11.18 The specificity of cell signaling
Figure 11.19 A scaffolding protein
Apoptosis
• Apoptosis - triggered by signals that
activate cell suicide
• In C. elegans (small worm), death
genes called ced. When activated they
stimulate death by activating proteases
and nucleases.
• Very similar genes found in other
animals including humans
• Apoptosis problems are associated with
cancer, Parkinson’s, and alzheimer’s