1
Q
Saccharomyces cerevisiae mating
A
- identify mates by chem signaling
- 2 mating types: a and alpha
- ‘a’ cells secrete a signaling molecule called ‘a factor’, which can bind to specific receptor proteins on nearby ‘alpha’ cells
- binding of the factors induces changes in the cells that lead to their fusion
2
Q
signal transduction pathway
A
- A series of steps linking a mechanical, chemical, or electrical stimulus to a specific cellular response.
- strikingly similar in yeast and mammals, bacteria and plants
3
Q
quorum sensing
A
- bacterial cells secrete small molecules that can be detected by other bacterial cells
- the concentration of such signaling molecules, sensed by the bacteria, allows them to monitor the local density of cells, a phenomenon called QUORUM SENSING
- allows bacterial populations to coordinate their behaviors so they can carry out activities that are only productive when performed by a given number of cells in synchrony – ex: biofilm
4
Q
cell-cell recognition
A
two cells in an animal may communicate by interaction btwn molecules protruding from their surfaces
5
Q
local regulators
A
- messenger molecules secreted by the signaling cell that travel only short distances
- influence cells in the vicinity
- ex: growth factors – compounds that stimulate nearby target cells to grow and divide
- numerous cells can simultaneously receive and respond to the molecules of growth factor produced by a single cell in their vicinity
6
Q
glycogen breakdown
A
- Sutherland studied how epinephrine, aka adrenaline, stimulates glycogen breakdown
- releases glucose 1-phosphate, which the cell (liver/muscle) converts to glucose 6-phosphate
- the cell can use this compound, an early intermediate in glycolysis, for energy production OR
- the compound can be stripped of phosphate and released from the cell into the blood as glucose, which can fuel cells throughout the body
- thus, 1 effect of epinephrine is the mobilization of fuel reserves
7
Q
Sutherland’s observations
A
- epinephrine stimulates glycogen breakdown W/O PASSING THRU PLASMA MEMBRANE by somehow activating a cytosolic enzyme, GLYCOGEN PHOSPHORYLASE
- but no breakdown occurred when epinephrine was added to a test-tube mixture of glycogen phosphorylase + glycogen – epinephrine could activate glycogen phosphorylase only when the hormone was added to a sol’n containing intact cells
- the binding of epinephrine to a receptor protein in a liver cell’s plasma membrane leads to activation of glycogen phosphorylase
8
Q
Sutherland’s 2 conclusions
A
- epinephrine doesn’t interact directly w/ the enzyme responsible for glycogen breakdown; an intermediate step(s) must be occurring inside the cell
- plasma membrane is somehow involved in transmitting the signal
9
Q
reception
A
- target cell’s detection of a signaling molecule coming from outside the cell
- a chem signal is ‘detected’ when the signaling molecule binds to a receptor protein
10
Q
transduction
A
- initiated when the binding of the signaling molecule changes the receptor protein in some way
- the transduction stage converts the signal to a form that can bring about a specific cellular response
11
Q
ligand binding
A
- generally causes a receptor protein to undergo a change in shape
- -> (most) shape change directly activates the receptor, enabling it to interact w/ other cellular molecules OR
- -> for others, the immediate effect is to cause the aggregation of 2 or more receptor molecules, which leads to further molecular events inside the cell
12
Q
GPCR
A
- G protein coupled receptor
- A signal receptor protein in the plasma membrane that responds to the binding of a signaling molecule by activating a G protein.
13
Q
G protein
A
A GTP-binding protein that relays signals from a plasma membrane signal receptor, known as a G protein-coupled receptor, to other signal transduction proteins inside the cell.
14
Q
GPCR structure
A
- they make up a large family of eukaryotic receptor proteins w/ a secondary structure in which the single polypeptide has SEVEN transmembrane ALPHA helices
- specific loops btwn the helices form binding sites for signaling and G protein molecules
15
Q
kinase
A
enzyme that catalyzes the transfer of phosphate groups
16
Q
RTKs vs GPCRs
A
for RTKs, a single ligand-binding event is able to trigger MANY pathways
17
Q
RTK structure
A
- before signaling molecule binds, the receptors exist as individual units (monomers)
- each monomer has an extracellular ligand-binding site, an ALPHA helix spanning the membrane, and an intracellular tail containing multiple tyrosines
18
Q
RTK
A
- receptor tyrosine kinases
- belong to a major class of plasma membrane receptors characterized by having enzymatic activity
19
Q
cancer
A
abnormal RTKs that function even in the absence of signaling molecules are associated w/ many types of cancer
20
Q
intracellular receptors
A
- found in cytoplasm/nucleus of target cells
- these chem messengers are able to pass thru the target cell’s plasma membrane b/c they’re either hydrophobic enough or small enough; ex: steroid hormones, thyroid hormones, nitric oxide
21
Q
protein kinase
A
An enzyme that transfers phosphate groups from ATP to a protein, thus phosphorylating the protein.
22
Q
RTK vs most protein kinases
A
- most cytoplasmic protein kinases act on proteins diff from themselves
- most phosphorylate either 2 of other amino acids, serine or threonine, rather than tyrosine
23
Q
phosphorylation
A
- each brings a shape change
- each shape change results from the interaction of the newly added phosphate groups w/ charged or polar amino acids
- often changes a protein from inactive –> active, but can decrease the protein’s activity
24
Q
PP
A
- protein phosphatases
- enzymes that catalyze the removal of the phosphate groups from the proteins (dephosphorylation), making them inactive and available for reuse
- provide the mechanism for turning off the signal transduction pathway when the initial signal is no longer present
25
second messengers
- small non-protein water-soluble molecules/ions involved in signaling pathways
- b/c they're small and water-soluble, they can readily spread throughout the cell by diffusion
- ex: cyclic AMP, Ca ions (Ca2+ more popular)
26
cAMP pathways
- cyclic adenosine monophosphate
- G proteins, GPCRs, protein kinases
- the immediate effect of cAMP is usually the activation of a serine/threonine kinase called PROTEIN KINASE A
- the activated protein kinase A then phosphorylates various other proteins
27
cAMP and epinephrine
- when epinephrine outside the liver cell binds to a specific receptor protein, the protein activates the enzyme ADENYLYL CYCLASE (embedded in plasma membrane), which in turn can catalyze the synthesis of many molecules of cAMP
- cAMP broadcasts the signal to the cytoplasm; doesn't last long b/c another enzyme, PHOSPHODIESTERASE, converts cAMP to AMP (another surge of epinephrine is needed to boost cAMP's cytosolic concentration again)
28
cholera
- Vibrio cholerae bacteria form a biofilm on the lining of the small intestine and produce a toxin
- this toxin is an enzyme that chemically modifies a G protein involved in regulating salt and water secretion
- the modified G protein is unable to hydrolyze GTP to GDP; it remains stuck in its ACTIVE form, continuously stimulating adenylyl cyclase to make cAMP
- the resulting high concentration of cAMP causes the intestinal cells to secrete large amounts of salts into the intestines, w/ water following by osmosis
29
cGMP
acts as a signaling molecule whose effects include relaxation of smooth muscle cells in artery walls
30
Viagra
- compound that inhibits the hydrolysis of cGMP to GMP, thus prolonging the signal
- originally prescribed for chest pains b/c it increased blood flow to the heart muscle
- leads to blood vessel dilation
31
other second messengers involved in Ca2+ release
inositol triphosphate (IP3) and diacylglycerol (DAG), produced by cleavage of the phospholipid PIP2 by phospholipase C
32
fine tuning: signal amplification
the amplication effect stems from the fact that these proteins persist in the active form long enough to process numerous molecules of substrate before they become inactive again
33
diverging pathway (produces 2 responses)
often involve RTKs (which can activate multiple relay proteins) or 2nd messengers (which can regulate numerous protiens)
34
scaffolding protein
A type of large relay protein to which several other relay proteins are simultaneously attached, increasing the efficiency of signal transduction.
35
WAS
- Wiskott-Aldrich syndrome; inherited disorder
- absence of a single relay protein; normally, it's located just beneath the cell surface; it interacts w/ microfilaments of cytoskeleton and w/ several diff components of signaling pathways that relay information from the cell surface
- effects: abnormal bleeding, eczema, predisposition to infections and leukemia
36
signal termination
- as the external concentration of signaling molecules falls, fewer receptors are bound at any given moment, and the unbound receptors revert to their inactive form
- cellular response occurs only when the concentration of receptors w/ bound signaling molecules is above a certain threshold
37
apoptosis
- cellular agents chop up the DNA and fragment the organelles
- cell shrinks and becomes lobed ("blebbing")
- the cell's parts are packaged up in vesicles that are engulfed and digested by specialized scavenger cells
- neighboring cells are protected from damage that they would otherwise suffer if a dying cell leaked out its concentrs, including its digestive enzymes
38
mitochondrial apoptotic pathway: intracellular signals
- from nucleus: generated from DNA has suffered irreparable damage
- from ER: when excessive protein misfolding occurs
39
apoptotic pathways in mammals
- certain mitochondrial proteins are triggered to form molecular pores in the mitochondrial outer membrane, causing it to leak and release other proteins that promote apoptosis
- these other proteins include cytochrome c, which functions in mitochondrial e- transport in healthy cells but acts as a cell death factor when released from mitochondria
40
C. elegans apoptotic genes
- ced-3 and ced-4: encode proteins essential for apoptosis; these and most other proteins involved in apoptosis are continually present in cells, but in in active form
- protein Ced-3 is the chief caspase in C. elegans.caspases are the main proteases of apoptosis.
- Ced-9 protein: in outer mitochondrial membrane; as long as it's active (inhibiting Ced-3 and Ced-4 activity), apoptosis is inhibited
