Final Exam Review Flashcards
What are the basic elements found in a cell signaling pathway
1) extracellular signal molecule
2) receptor protein
3) intracellular signaling proteins
4) effector proteins
Note: signalling molecules don’t go through the cell membrane. The protein transduces the signal, and it goes through lots of different proteins before it reaches the part that has an effect.
What kinds of extracellular signalling molecules are there, and what range do they work on?
1) Contact-dependent
2) Paracrine
3) Synaptic
4) Endocrine
How do different signalling processes take effect
Protein changes (i.e. kinases causing phosphorylation) happen very quickly while alterations to DNA expression take a much longer time (comparatively). If each reaction takes the same amount of time, signal to phosphorylation is a few reactions, while signal to transcription to translation is at least an order of magnitude more complicated.
GPCRs tend to be very fast, while enzyme-couple reactors tend to be slower and signal for things like growth, proliferation, and differentiation
Intracellular signaling complexes
Classes of cell-surface receptors
1) ion-channel-linked receptor
2) g-protein linked receptor
3) enzyme-linked receptor
Phospholipase C signaling pathway
Phospholipace C: Enzyme associated with the plasma membrane that generates two small messenger molecules in response to activation.
Once activated, Phospholipase C propagates the signal by cleaving a lipid molecule (inositol phospholipid) that is a component of the plasma membrane.
Cleaving this molecule results in two second messenger molecules: diacylglycerol and inositol triphosphate (IP3). IP3 is released into the cytosol, and it binds to an opens calcium channels in the ER, letting calcium rush out into the cytosol. The calcium signal other molecules in the cell.
Diacylglycerol remains embedded in the plasma membrane. It recruits and activates a kinase (protein kinse C) which needs to bind to calcium to become active. Once it is active, it phosphorylates various intracellular proteins depending on the cell type.
Ras mutation
Components of intracellular signaling pathways
1) Relay the signal onward. Scaffold proteins assist by bringing together necessary components to propagate the signal
2) Amplify the signal received. A few extracellular molecules are enough to have a large intracellular response
3) Integrate: they can detect signals from more than one pathway and integrate them before relaying a signal onward
4) Distribute: The can distribute the signal to more htan one effector protein, creating branches in the information flow diagram and evoking a complex response
5) Feedback: They can modulate the response to a signal by regulating the activity of components upstream in the signaling pathway (it can weaken or enhance the signalling)
G-protein couple receptors:
Form the largest family of cell-surface receptors, many drugs work through GPCRs.
An extracellular signal causes the protein receptor to activate a G protein located on the cytosolic side of the plasma membrane.
Unstimulated: GDP is bound to it, and the G protein is idle.
When the signalling protein binds to it, it alters so that the alpha subunit decreases its affinity for GDP, and so exchanges it for GTP.
The signal stays on until the alpha protein hydrolyzes its GTP to GDP, returning it to the original inactive state.
How diseases can affect GPCRs
Cholera enters intestinal cells and modifies the alpha subunit so that it can no longer hydrolyze its GTP, locking it into an active state. This causes the cell to continuously secrete water and CL- into the intestine.
Pertussis disable the GPCR by locking it into its GDP-bound state, making it always inactive. This signaling pathway is supposed to inhibit coughing, so when it is shut down, coughing is no longer inhibited.
Enzyme-coupled receptors/ Receptor Tyrosine Kinases
Often signal things like growth, survival, differentiation, proliferation, migration, etc, so mutations in these proteins are hallmarks of cancer cells.
Generally work when a signalling molecule causes two receptor molecules to come together and become dimerized. This activates their kinase domains, and the receptors phosphorylate each other. These phosphorylated tyrosine tails bind to and activate a whole cascade of other proteins. This lets them transmit the signal to numerous different pathways, allowing for a complex reaction to a signal. One of the proteins that is most commonly activated by RTKs is Ras.
Ras
One of a large family of small GTP-binding proteins that helps relay signals from cell-surface receptors to the nucleus. Many human cancers contains an overactive mutant form of the protein.
Active when GTP is bound to it, and inactive when GDP is bound to it. RasGEF encourages Ras to exchange its GDP for GTP, activating Ras. Ras GAP promotes the hydrolysis of the GTP, turning RAS back into its inactive state. Activated Ras causes a signaling cascade that encourages proliferation (the exact outcome differs depending on various other signals also present in the cell.)
A mutant version of Ras inactivates the GTPase activity of Ras, so that it can’t shut itself off and it always active. This is found in about 30% of cancer cells.
Issues with Ras signaling
Three types of cytoskeleton filaments
Intermediate filament construction
Intermediate filaments are connected to each other and to proteins in the membrane so they can connect intercellularly and provide strength across cells.
Structure of microtubules
Dynamic instability of microtubules
Motor proteins that determine the direction of transport
Kinesins: mostly move towards the plus end of a microtubule
Dyneins: mostly move towards the minus end of a microtubule.
They both have ATP dependent globular heads that cause the movement, and both attach to the microtubules in only one direction.
Actin filaments
Anchoring the cytoskeleton
Movement of cilia and flagella
Both contain stable microtubules that are moved by dynein, and the movement is produced by the bending that takes place as the microtubules slide against each other.
What causes muscle contraction?
It is caused by a myosin filament that is basically shaped like a double-ended arrow. The myosin heads on either end point in different directions. It then pulls actin filaments in opposite directions at either end (in towards the middle)
myofibrils
long cylindrical structure that constitutes the contractile element of a muscle cell. Its constructed of arrays of highly organized bundles of actin, myosin, and accessory proteins.
Made of a chain of identical tiny contractile units called sarcomeres. These give the myofibrils their striped appearance
sarcomeres
Highly organized assembly of actin and myosin filaments that serve as the contractile unit of a myofibril in a muscle cell.
Mechanism of muscle contraction
Triggered by a rudden rise in cytosolic calcium. The neurotransmitter from a nerve cell triggers an action potential in the muscle cell plasma membrane. The elctrical ecitation spreads along the transverse tubules that extend inwards from the plasma membrane. This signal is passed to the sarcoplasmic reticulum (vesicles that contain a high concentration of Ca+ molecules.) The electrical excitation causes the sarcoplasmic reticulum to release into the cytosol. The calcium binds to troponin, which then causes tropomyosin to shift its position, letting the myosin heads bind to the actin filaments, initiating contraction.
When a muscle cell is stimulated to contract, the mysoin heads walk along the actin filaments in cycles of attachment and detachment, using ATP. After the contraction is completed, the myosin heads lose contact with the actin filaments, causing the muscle to relax.
What are the four phases of the eukaryotic cell cycle?
How does cyclin concentration affect the cell cycle MORE INFO NEEDED
How does DNA damage block the progression of the cell cycle?
What are the phases of mitosis?
How does the mitotic spindle work? MORE INFO NEEDED
Three classes of extracellular signal molecules
Extrinsic pathway of apoptosis
Comparison of mitosis and meiosis
Comparison of the steps of mitosis and meiosis
Introduction to inheritance
note: dominant mutation does not mean wildtype, those are two different things
recessive means the phenotype only shows when the organism has both copies of the recessive allele
What does the second generation (F2) of a dihybrid cross look like?
note: it is important that Mendel picked traits that are independent of each other (inherited separately)
Differentiation of human tissues
Take-away: every cell we have comes from a zygote, that zygote is totipotent because it can create a whole person
Pluripotent means it can develop into different tissues
induced pluripotent stem cells
Two major classes of cancer-related genes
Two major classes of cancer-causing mutations
Possible exam question: would the phenotype of this mutation follow the mutated gene or follow the wild type?
Ras mutation in cancer
Mutated ras (so that it is always active) will be dominant
Rb mutation in cancer
Rb only lets s phase go foward when the right signals are there. When it is mutated so that it can no longer be expressed, the cell will always be going forward with s phase when it shouldn’t. One good copy should still allow it to be expressed, so it would likely need both copies mutated to stop suppressing signals to go into s phase.
examples of different Rb mutations and whether they result in cancer
