Cell Signalling Flashcards
What are paracrine and autocrine signaling?
Paracrine signaling occurs when a cell secretes a signaling molecule ( a ligand) which binds to a receptor on an adjacent or very nearby cell. Autocrine signaling occurs via the same process but involves a receptor on the same cell that secreted the signal.
What is contact dependent signaling and where does it occur?
Contact dependent signaling occurs when a cell displays but does not release a ligand on its outer membrane that bind to a receptor on another cell. Occurs in immune response.
What is endocrine signaling?
Endocrine signaling occurs when a cell secretes a signaling molecule that enters the blood stream and exerts and effect on distant cells in the body. Hormones are endocrine signals.
What is synaptic signaling?
Synaptic signaling occurs in the synaptic cleft between neurons and target cells. It occurs over a very small distance but transmits signals between very distant cell bodies.
What are the two primary classes of signaling molecules and what are their relative properties?
Lipophilic and hydrophilic
Lipophilic signals can cross membranes, so their receptors may locate anywhere in the cell, but they can only be controlled through transription (slower response)
Hydrophilic signals cannot cross membranes, so their receptors must be membrane bound, they can be produced and stored in vesicles with regulated release (fast acting)
What is the general pathway of cell signaling?
Signal molecule binds to receptor molecule
Receptor molecule initiates a series of intracellular signaling molecules leading to the activation of different metabolic, gene expression, cellular structure, or exo/endocytosis machinery (cell signals can affect nearly every aspect of a cell)
What are two methods of regulation of cell signaling?
Regulation of release of signaling molecules.
Regulation of expression of receptor molecules.
How do synaptic receptors trigger muscle contraction?
Ligand-gated Na+ channels bind with a Neurotransmitter (Acetylcholine) and open, allowing influx of Na+ and depolarizing the cell. This leads to the opening of VGNa+ channels and the triggering of an action potential that results in Ca2+ influx to the cytoplasm from the exterior and the sarcoplasmic reticulum (involving invaginated Ca2+ channels). Cytoplasmic Ca2+ causes muscle contraction.
Name 4 different types of cell signal receptors located on the cell surface.
Ligand Dependent Ion Channels (LDC)
Voltage Dependent Ion Channels (VDC)
G-Protein-Coupled Receptors
Enzyme Linked Receptors
Name two types of cell signal “receptors” that do not locate to the extracellular membrane.
“Nuclear” Receptors - found in the cytosol, may enter the nucleus only when bound to their ligand (always lipophilic ligands), may also have other cytosolic processes
Metabolic sensing - process by which beta-cells detect glucose levels and secrete insulin, not technically a receptor.
Two types of second messengers systems and examples of crosstalk between the systems.
1 Ca2+ - influx of extracellular Ca can release intracellular Ca
2 G-Protein-Coupled Receptors often link to second messengers including Phospholipase-C (DAG & IP3), Adenylyl Cyclase (cAMP), Guanylyl Cyclase (cGMP)
3 Crosstalk between GPC 2nd messengers and Ca channels releases more Ca, and Ca can trigger cAMP, cGMP, and Nitrous Oxide production.
What are processes do cell signaling pathways ultimately cause?
Phosphorylation Acetylation Glycosylation Ubiquitinylation Proteolytic cleavage Protein-Protein binding
Because signal transduction usually involves signal amplification, how is this amplification achieved?
Positive feedback loops: Ca2+ influx triggers Ca2+ release from SR (also coupled to negative feedback loop to moderate the effect).
Signaling cascades: amplification depends on how many downstream molecules are activated and how long these molecules remain activated.
How is signaling terminated?
Extracellular signaling may be diminished through reduced concentration, inactivation, or uptake by transporters
Receptors may be desensitized, reduced transmission of signal, or internalization
2nd Messengers may be diminished, Ca2+ sequestration, cAMP or cGMP modified to AMP or GMP
Phosphorylation/dephosphorylation may be reversed.
In what process does phosphodiesterase PDE5 function?
The transformation of cGMP to GMP. Always active in the presence of cGMP, it also binds cGMP to a non-catalytic site which enhances its catalytic activity. cGMP also activates PKG, which phosphorylates PDE5 and further enhances its catalytic activity. This is an example of cooperativity in enzyme kinetics, producing an S-shaped curve in a Michelis-Menton plot.
