CAMPBELL & REECE CHAPTER 11 CELL COMMUNICATION. Cell Messaging some universal mechanisms of cellular...
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CAMPBELL & REECE CHAPTER 11 CELL COMMUNICATION
CAMPBELL & REECE CHAPTER 11 CELL COMMUNICATION. Cell Messaging some universal mechanisms of cellular regulation cells most often communicate with other
Cell Messaging some universal mechanisms of cellular regulation
cells most often communicate with other cells by chemical
signals
Slide 3
Evolution of Cell Signaling Yeast: Saccharomyces cerevisia 2
sexes: a & type a secrete a signaling molecule called a factor
which can bind to receptor proteins on cells @ same time cells
secrete factor which binds to receptor proteins on type a
cells
Slide 4
Saccharomyces cerevisiae 2 mating factors then cause the 2
yeast cells to grow toward each other & initiate other cell
changes results in fusion or mating of 2 cells of opposite type a/
cell that contains genes of both original cells this new cell later
divides passing this genetic combination to their offspring
Slide 5
Signal Transduction Pathway series of steps initiated by signal
molecule attaching to receptor mechanism similar in yeasts and
mammals & between bacteria and plants Scientists think
signaling mechanisms 1 st evolved in ancient prokaryotes &
unicellular eukaryotes then adopted for new uses by their
multicellular descendants
Slide 6
Communication Among Bacteria quorum sensing: bacteria release
small molecules detected by like bacteria: gives them a sense of
local density of cells allows them to coordinate activities only
productive when performed by given # in synchrony ex: forming a
biofilm: aggregation of bacteria adhered to a surface: slime on
fallen leaves or on your teeth in the morning (they cause
cavities)
Slide 7
Biofilm Developing
Slide 8
Biofilm Development
Slide 9
Local Signaling (eukaryotic cells can also use cell junctions)
secretion of chemicals = messenger molecules from signaling cell
messenger molecules that travel to nearby cells only called: local
regulators
Slide 10
Local Regulators Animals: use 1 class of local regulators:
growth factors many cells in neighborhood respond to growth factor
produced by 1 cell paracrine signaling: secreting cell acts on
nearby target cells by discharging local regulator
Slide 11
Paracrine Signaling
Slide 12
Synaptic Signaling in the animal nervous system action
potential travels thru cell membrane of neuron when the electrical
signal reaches axon end it triggers exocytosis of neurotransmitter
(messenger molecule) neurotransmitter travels across small space
(synapse) attaches to receptors on target cell
Slide 13
Synaptic Signaling
Slide 14
Local Signaling in Plants not as well understood as in animals
use hormones (as do animals): long distance signaling aka endocrine
signaling travel target cells (any cell that has receptor for
hormone) Plant hormones aka plant growth regulators most reach
their targets by moving cell-to- cell some travel in vessels
Slide 15
Long Distance Signaling hormones (in some cases)
neurotransmitters: electrical signal travels length of neuron, may
go from neuron-to- neuron for long distances ability for any cell
to respond to messenger molecule requires cell to have receptor for
that particular molecule
Slide 16
Slide 17
3 Stages of Cell Signaling 1. Reception target cells detection
of the signal 2. Transduction receptor protein changes converting
signal to a form that can bring about specific cellular response
via a signal transduction pathway 3. Response activation of
cellular response
Slide 18
Stages of Cell Signaling Response
Slide 19
Slide 20
Reception cells must have a receptor for the ligand (messenger
molecule) to react with many signal receptors are transmembrane
proteins with water-soluble ligands ligands: usually large
hydrophilic
Slide 21
Membrane Receptors
Slide 22
G-Protein-Coupled Receptors cell-surface transmembrane receptor
works with help of a G protein (protein that binds to GTP) flexible
inherently unstable difficult to crystallize so can study structure
(use x-ray crystallography)
Slide 23
G Protein-Coupled Receptor: 7 helices
Slide 24
Slide 25
Receptor Tyrosine Kinases major class of membrane receptors
w/enzyme activity kinase: enzyme that catalyzes addition of
phosphate group cytoplasmic side of receptor has enzyme that:
phosphate group from ATP tyrosine (on substrate protein)
Slide 26
Tyrosine
Slide 27
Inactive Monomers of Tyrosine Kinase When there is no ligand
attached to receptor site the kinase receptor protein exists as
monomers
Slide 28
Binding of Signaling Molecule: Form Dimers
Slide 29
Tyrosine Kinase Activated by Dimerization phosphate group added
to each tyrosine
Slide 30
Slide 31
Recognition by Relay Proteins Relay proteins attach to
phosphorylated tyrosine structural change that activates the bound
protein Each activated relay protein triggers different
transduction pathway specific cellular response
Slide 32
Slide 33
ION CHANNEL RECEPTORS Ligand-Gated Ion Channels
Slide 34
Ligand Binds to Receptor Site ion crosses membrane & enters
cytoplasm transduction pathway leading to a response
Slide 35
Ligand Dissociates from Receptor Site
Slide 36
Intracellular Receptors in cytoplasm or nucleus of target cells
hydrophobic or very small ligands examples steroid hormones &
thyroid hormones of animals NO (nitric oxide), a gas
Slide 37
Slide 38
Turning on Genes special proteins called transcription factors
control which genes are turned on example: Testosterone (steroid
hormone) its activated receptor acts as transcription factor that
turns on specific genes thus activated receptor carries out
transduction of the signal
Slide 39
Slide 40
TRANSDUCTION when receptors for signaling molecules are
membrane proteins the transduction stage is multistep pathway
usually involves inactive/active state by adding/removing phosphate
group benefit of multistep pathway is that possibility of
amplification of signal if each step on pathway can transmit signal
to several molecules end up with large # activated molecules @ end
of pathway
Slide 41
Signal Transduction Pathway in most cases original signaling
molecule does not enter cell & is not passed along signaling
pathway 1 st step triggered by signaling molecule binding to
receptor proteins often used as relay molecules (protein
interaction a unifying theme of all cellular regulation)
Slide 42
Protein Phosphorylation & Dephosphorylation protein kinase:
enzyme that transfers phosphate groups from ATP protein most act on
proteins different than themselves most act on a.a. serine or
threonine (not tyrosine as in previous example) includes kinases in
plants, animals, & fungi many relay molecules in pathway are
kinases
Slide 43
Phosphorylation Cascade
Slide 44
Protein Phosphatases enzymes that can rapidly remove phosphate
groups from proteins (inactivating them) also make kinases
available to reuse this phosphorylation/dephosphorylation system
acts as molecular switch in cell position of the switch @ any given
time depends on balance between active kinase & active
phosphatase molecules
Slide 45
Slide 46
Second Messengers many signaling pathways involve small,
nonprotein, water-soluble molecules or ions known as 2 nd
messengers 1 st messenger is extracellular signaling molecule 2
most widely used 2 nd messengers are cAMP & Ca++
Slide 47
Cyclic AMP epinephrine causes glycogen in hepatocytes to
glucose w/out entering cells search for 2 nd messenger that
transmits signal from plasma membrane metabolic pathway in
cytoplasm epinephrine binding to receptor followed by elevation of
cytosolic concentrations of cAMP
Slide 48
cAMP
Slide 49
ATP cAMP
Slide 50
Adenylyl Cyclase enzyme embedded in plasma membrane ATP cAMP in
response to extracellular signals directly or
indirectly(epinephrine one of many) indirectly: receptor protein
changes when signaling molecule attaches activates many adenylyl
cyclase possibly thru GTP
Slide 51
Slide 52
GTP
Slide 53
cAMP as 2 nd Messenger 1 st messenger activates G protein-coup-
led receptor adenylyl cyclase ATP to cAMP activates another protein
(usually protein kinase A)
Slide 54
Protein Kinase A serine/threonine kinase once activated it will
phosphorylate other proteins (depends on cell type)
Slide 55
Slide 56
Other Regulation Mechanisms G protein systems inhibit adenylyl
cyclase uses different signaling molecule & receptor
Slide 57
understanding role of cAMP helps to explain how certain
microbes cause disease Vibrio cholerae: causes cholera in
contaminated water forms biofilm over small intestines produces a
toxin: enzyme that chemically modifies a G protein involved in
regulation of water & salt secretion (GTP --/ GDP so protein
stays stuck in active form) high [cAMP] cells secrete large amts
salts followed by water (osmosis)
Slide 58
Vibrio cholerae
Slide 59
Calcium Ions many signaling molecules induce responses in
target cell using signal transduction pathways that increase
intracellular [Ca++] more widely used than cAMP as 2 nd
messenger
Slide 60
Animal Cells Plant Cells contraction secretion cell division
pathway that leads to greening in response to light Effects of
Ca++
Controlling Response generally, response controlled @ >1
site (not just either on or off) 4 aspects of fine-tuning response:
1. Signal amplification 2. Specificity 3. Efficiency 4. Termination
of signal
Slide 74
Signal Amplification enzyme cascades amplify the cells response
to a signal @ each step the # of activated products much > in
preceding step of cascade amplification happens because activated
protein kinase stays in activated form long enuf to process
numerous molecules of substrate as result a small # signal
molecules (like epinephrine) can release 100s of millions of final
product (glucose molecules)
Slide 75
Slide 76
Specificity of Cell Signaling & Coordination of the
Response certain cells respond to some signals & have no
response to others 2 different cells may have different responses
to same signal different kinds of cells turn on different genes so
different kinds of cells have different collections of
proteins
Slide 77
What controls responses in cells? response of a particular cell
to a signal depends on its particular collection o 1. signal
receptor proteins 2. relay proteins 3. proteins necessary to carry
out the response
Slide 78
Slide 79
Signaling Efficiency: Scaffolding Proteins & Signaling
Complexes Scaffolding Proteins: type of large relay protein to
which several other relay proteins are simultaneously attached
increasing the efficiency of signal transduction
Slide 80
Scaffolding Proteins Respond to same Signal
Slide 81
Scaffolding Proteins some are permanently held together
(terminal axons in neurons)
Slide 82
Relay Proteins that are Branch Points Wiskott-Aldrich Syndrome
(WAS) defect in single relay protein leads to: abnl bleeding eczema
predisposition to: infections leukemia
Slide 83
Termination of the Signal ability of cell to respond to new
signals depends on reversibility of changes produced by prior
signals binding of signal molecules to receptors is reversible as
[signal molecules] decreases fewer receptor sites occupied by
signal those unoccupied: receptor molecule reverts to its inactive
form
Slide 84
Termination of Signal any particular cell response occurs only
when concentration of occupied receptors has reached a certain
threshold: if below threshold the cell response stops relay
molecules return to inactive form cAMP AMP phosphorylated kinases
lose phosphate group
Slide 85
Slide 86
Apoptosis integrates multiple cell- signaling pathways
apoptosis: programmed cell death Steps: 1. DNA gets copped up into
pieces 2. organelles & other cytoplasmic components fragment 3.
cells parts put into vesicles which are engulfed by phagocyctic
cells 4. blebbing occurs (cell becomes multilobed)
Slide 87
Apoptosis in Soil Worm C. elegans 2 genes identified Ced4 &
Ced3 (ced for cell death) both encode for proteins essential for
cell death are always present in a cell in inactive form C. elegans
has protein in outer mitochondrial membrane called Ced9 (from gene
of same name) which serves as master regulator of apoptosis (has
its brake on until death signal overrides it)
Slide 88
Slide 89
Signals that Trigger Apoptotic Pathways capase: group of
proteins that mediate apoptosis several different pathways
involving 15 capases identified in mammals which pathway used
depends on type of cell & signal used 1 major pathway involves
mitochondrial proteins that form pores in mitochondrial membrane
releasing mitochondrial proteins, including cytochrome c, activate
capases