Seminar 12: Cell sensing & responding to the environment Flashcards
what are the steps of cell to cell communication?
- Signal perception
a. Comes from outside cell, usually a chemical signal- Intracellular signal transduction
a. Binding of signalling molecule to receptor protein (on surface OR inside cell)
b. Changes tertiary structure of protein, initiates transduction
c. Transduction stage : converts signal from molecule TO FORM that can BRING ABOUT specific cellular responses
i. Can occur in 1 STEP, but usually occurs in SEQ OF CHANGES in DIFF molecules (Signal transduction pathway) - Cellular response
a. Final stage
b. When transduced signal finally triggers a cellular specific response
i. E.x catalysis by enzyme, rearrangement of cytoskeleton, activation of gene etc
- Intracellular signal transduction
function of cell signalling process?
ensure that crucial activities occur in the RIGHT cells @ the RIGHT TIME & in PROPER COORDINATION w/ other activities happening w/in the cell
what is signal transduction
1 type of signal converted to another
- Target cell converts EXTRACELLULAR SIGNAL MOLECULE into INTRACELLULAR SIGNALLING MOLECULE
Explain why each hormone specifically affects one cell type and not others.
Each cell has receptors for the hormones needed to signal changes in that cell and lacks receptors for hormones not needed for signalling changes. Each receptor has a specific shape and molecular makeup that recognizes and binds to one specific hormone. This enables cells to respond only to hormones that are of importance to those cells’ functions
define autocrine signalling
- cell > cell comm
- signals affect the cells that made them
- bind only to receptors on the same cell that made it (causes change in cell activity)
define Juxtacrine signalling
- cell > cell comm
- signals affect only adj cells
- ligand on 1 cell interact w/ receptor on adj (direct contact)
define paracrine signalling
- cell > cell comm
- signals affect nearby cells of gland secreting it
define hormones signalling
travel to distant cells, usually via the circular system (bloodstream)
desc how intracellular receptors work
- NP &/or SMALL signal (can diffuse through bilayer)
- binds to receptor in cytosol causing CHANGE in SHAPE (allows signal to be give)
- causes cellular response to occur
desc how membrane receptors work
- LARGW &/or POLAR (can’t diffuse thru bilayer)
- receptor binding site on the top surface to allow for binding (connected to inside & outside of cell)
- ligand fits into receptor, causes CHANGW in protein conformation (leads to CHANGE INSIDE cell)
desc the way an enzyme-linked receptor creates a cellular response & GIVE EX
- receptor is extracellular but embedded in bilayer (connected to in&outside of cell)
- when ligand binds to it, causes conformational change to the receptor
- change transmits a SIGNAL to other molecules in pathway (e.x insulin response substrate)
- signal causes phosphorylation of an INTERNAL protein (triggers cascade of chemical responses w/in cell)
e.x: insulin receptor
desc the way a GPCR receptor works & ex
- embedded in plasma membrane (contact w/in&outside cell)
- works via an intermediary (G protein)
- ligand (hormone) binds to the receptor, to ACTIVATE the G protein (GDP connected is phosphorylated to GTP, now ACTIVE)
- Activated G protein SUBUNIT ACTIVATES EFFECTOR protein
- GTP hydrolysed back to GDP to activate
- ACTIVATED effector protein can now cause cellular responses
e.x: epinephrine receptor
desc the way ligand-gated ion channel receptors work & give e.x
- embedded in bilayer
- when activated (ligand binds), ion channel changes shape (opens, ions can pass)
- channel is lined with charged ions that allow ions of OPPOSITE CHARGE to flow into cell
e.x: Acetylcholine receptor
desc an intracellular receptor & give e.x
- INSIDE cell (cytosol, nucleus)
- turn ON transcription of specific genes
- can only interact w/ NP&/or small ligands (diffused thru bilayer on its own)
- ligand binds to receptor & chaperone protein complex
- causes receptor to CHANGE shape, releases chaperone
- receptor & ligand complex enter nucleus (because CORRECT shape)
- initiate cellular response (transcription of particular gene)
e.x: estrogen receptor
what are the 4 diff ways cells initiate cellular responses?
- relay signal onward & help it to spread through a cell
- AMPLIFY the signal received (stronger) so that a FEW extracellular ligands are ENOUGH to evoke a LARGE INTRACELLULAR response
- DETECT signals from 1+ intracellular signalling pathway & INTEGRATE them before RELAYING a signal onward
- DISTRIBUTE the signal to 1+ effector protein, creating braches in flow diagram to evoke a COMPLEX response
How is it a benefit to the cell to have so many protein kinase molecules participating in the signal transduction pathway shown?
The protein kinase cascade provides a means for amplifying the signal so that a single signal molecule can cause many thousands of molecules to be activated at the end of the pathway as part of the cellular response.
what is crosstalk
interactions b/w diff signal transduction pathways
what can crosstalk result in
- activation of 1 pathway / inhibition of another
under what CONDITIONS would autocrine signalling be most adv for a cell?
- imp for cell to maintain a specialised role
- e.x: cell might receive signal to specialise & form a tissue of many cells
- 1st cell would SELF-STIMULATE to GROW & DIVIDE to form tissue in response to SELF-SIGNALING
is binding of ligand > receptor covalent or non covalent & WHY
non covalent
- because only IM forces form between the site of the receptor & the ligand
- H bond, VDW, LDF, DF
what is the dissociation constant (KD)
- measure of the affinity of the receptor for its ligand
- lower KD = HIGHER AFFINITY of ligand > receptor
- low KD values allow receptors to bind to their ligands even at very low [ ligand ]
why is it important that binding of receptor & ligand is REVERSIBLE
- if ligand was never released, receptor would CONSTANTLY be stimulated, cell WON’T STOP RESPONDING
desc Agonists
- resemble the ligand & bind to the receptor
- set a receptor into signal transduction mode like the ligand does
desc Antagonists
- inhibitors
- bind > receptor & freeze it in place
- prevents real ligand from binding
- doesn’t set off signal transfuction
desc caffeine as antagonist
- similar molecular struc as adenosine
- adenosine acts as ligand > nerve cells (initiates signal transduction path = red brain activity, tiredness)
- caffeine binds to receptor, prevents adenosine binding
- allows nerve cell activity & active feeling to occur
desc G proteins (how many pp subunits, what molecules it binds)
- 3 pp subunits
binds: - receptor
- GDP & GTP
-effector protein
how is G protein replenished?
- inactive G protein (hydrolysed back to GDP) separates from effector protein
- diffuses in the membrane & binds to other 2 subunits
- G protein is reassembled, can act as binding agent again
what are mitogens
ligands that stimulate cell division/mitosis
4 reasons why PROTEIN KINASE CASCADES are USEFUL
- @ each step in cascade, signal is AMPLIFIED, becuz each newly activated kinase = enzyme that can catalyse PHOSPHORYLATION of MANY target proteins
- info from a signal that arrived @ membrane is communicated > nucleus (expression of MULTIPLE genes is MODIFIED)
- Multitude of steps = specificity to process
- Diff target proteins @ each step = VARIATION in RESPONSE
desc the func of a second messenger
- transmit the signal from the 1st messenger (ligand)
- AMPLIFY & DISTRIBUTE the signal
- leads to ACTIVATION of MANY enzyme targets
- involved in CROSSTALK
how are signal transduction pathways REGULATED?
- differ conc of 2nd messengers
- differences in conc of single component w/in pathway
- differences in conc of enzymes which change target molecules
what are the 3 main effects of a signal on cell function?
- opening of ion channels
- changes in enzyme activity
- differential gene expression
which methods of cell response to signalling are faster & which are slower? explain
ion-channel opening & enzyme modification are rapid
changes in gene expression AREN’t because they involve MANY steps, so this method is slower
what are gap junctions & what is their func
channels b/w adjacent cells in animals
- allow cells packed together to communicate directly w/ adj cells
what are connexons & what are they made of?
channel structures which gap junctions use to cross the space b/w cell membranes of adj cells
- 6 subunits pf connexin protein
what are plasmodesmata
- gap junction equiv for plants
- membrane lined tunnels that separate plant cells from one another
- channel wall is made of INTEGRAL MEMBRANE PROTEINS (from adj ce,, membrane)
why are plasmodesmata imp in plants?
- their vascular system LACKS tiny vessels (humans: capillaries for gas & nutrient transport)
- plasmodesmata = rapid diffusion
what is the difference b/w activation of a molecule by protein kinase & one by cAMP
- protein kinase activation occurs by a COVALENT change = phosphorylation
- cAMP activation occurs by NON COVALENT bonding
what would happen if there was no multi step signal transduction pathway
- not enough molecules of the final enzyme could be activated
- becuz each step of the pathway amplifies the signal as a kinase can act on MANY targets
