Cell Signaling Flashcards

Cell Signaling Basics

• Cell signaling is fundamental for cell communication.
• A receptor (on the cell surface or inside the cell) binds to a molecule secreted by or on the surface of another cell.
• This binding leads to a biological change, like altering gene expression or modifying protein function.
• Occurs across organisms (bacteria to animals), though the examples in the chapter focus on animals.
• Downstream biological effects: changes that occur in the cell after the signaling event.

Four Categories of Cell Signaling

1. Endocrine Signaling

• Hormone produced in a gland travels through the bloodstream.
• Binds to a receptor on the target cell, causing biological changes.
• Long-distance signaling.

2. Paracrine Signaling

• Cells in the local environment secrete a signal that binds to a receptor on a target cell.
• Leads to changes in gene expression or protein function.
• Short-distance signaling.
• The chemical signal secreted only stays in the local environment and does not travel through the bloodstream.

3. Neuronal Signaling

• Depolarization of the neuron's plasma membrane travels along the axon to the nerve termini.
• Neurotransmitters are released, travel through the synaptic cleft, and bind to receptors on the target cell.
• Elicits a biological change (e.g., depolarizing the membrane).
• Example neurotransmitter: Acetylcholine.

4. Contact-Dependent Signaling

• Target cell has a receptor on its surface.
• Signaling cell has a signaling molecule on its surface.
• Interaction between the signaling molecule and the receptor elicits a biological change in the target cell.
• Requires physical contact between the cells.
• The signaling molecule is bound to the plasma membrane of the signaling cell.

Panacrine vs Contact Dependent

• Panacrine and endocrine are similar except Panacrine stays local.
• Contact-dependent involves a signaling molecule on the cell surface; the cell itself acts as the signaling molecule.

Location of Receptors

• Messengers can interact with membrane receptors (on the cell surface) or intracellular receptors (inside the cell).
• Membrane receptors bind large, hydrophilic molecules that can't cross the plasma membrane.
• Intracellular receptors bind small, hydrophobic molecules that can cross the plasma membrane.
• The ultimate effect is a change in gene expression or protein function.

Neurotransmitters and Different Effects

• A single neurotransmitter can have different effects depending on the target cell and its receptors.
• Acetylcholine example:
  • Heart muscle: Decreases heart rate.
  • Salivary glands: Secretes digestive enzymes.
  • Skeletal muscle: Contracts.

Signal Combinations

• Cells receive multiple signals at any given time.
• Different combinations of signals lead to different cellular responses.
  • A, B, C signals: Cell stays alive.
  • A, B, C, D, E signals: Cell grows and divides.
  • A, B, C, F, G signals: Cell differentiates.
  • No A, B, C signals: Cell undergoes apoptosis (programmed cell death).
• Signaling pathways are integrated.

Response Time

• Changing gene expression takes longer than modifying protein function.
• Phosphorylating a protein: Seconds to minutes.
• Producing a metabolic enzyme: Minutes to hours.

Intracellular Cascades/Signaling Pathways

• A signal molecule binds to a receptor.
• Activates various proteins inside the cell.
• A cascade or pathway of interacting proteins leads to the ultimate cellular response.
• Can activate a metabolic enzyme, change the cytoskeleton, or turn on transcription.
• Signaling cascades often interact with each other.

Signal Transduction Overview

• A ligand binds to a receptor protein.
• The signal is relayed through the cell via a series of proteins.
• Secondary messengers (e.g., cyclic AMP) amplify and spread the signal.
• Integration: Different pathways converge.
• Feedback: Signaling further down the pathway can modify signaling earlier in the pathway.
• Distribution: The signal is distributed to the appropriate targets (proteins or genes).

Positive and Negative Feedback

• Positive Feedback: Signal from the end of the pathway tells an earlier step to amplify the signal.
• Negative Feedback: Signal from the end of the pathway tells an earlier step to stop the signal because there is enough.

Molecular Switches

• Proteins are turned on or off to transmit signals.

1. Phosphorylation

• Kinase phosphorylates a protein, generally turning it on.
• Phosphatase removes the phosphate group, turning the protein off.
• Cycles on and off.
• Kinases have specificity for certain amino acids:
  • Serine/Threonine kinases: Add a phosphate group to serine or threonine.
  • Tyrosine kinases: Add a phosphate group to tyrosine.

2. GTP-Binding Proteins

• When bound to GTP, the protein is active.
• When GTP is hydrolyzed to GDP, the protein is inactive.
• GAPs (GTPase-activating proteins) cause dissociation.
• GEFs (Guanine nucleotide exchange factors) cause association.
• Cycle between active and inactive states.

Receptor Types

1. Ion Channel Receptors

• A signal molecule binds to an ion channel, opening it.
• Ions flow in, depolarizing the membrane and propagating the signal.

2. G Protein-Coupled Receptors (GPCRs)

• Seven-transmembrane receptor associated with a trimeric G protein.
• Signal molecule binds, causing conformational changes in the receptor.
• Activates the G protein, initiating signal transduction.
• Structure: Seven transmembrane loops.
• Ligands: Proteins, peptides, amino acid derivatives, or fatty acids.
• G Protein Activation Stages:
  1. Inactive receptor and trimeric G protein (alpha, beta, gamma subunits).
     • Alpha subunit interacts with GTP or GDP.
     • Beta and gamma subunits stay together.
  2. Signal molecule binds, causing GDP dissociation and GTP binding to the alpha subunit. Activated G protein can activate other G proteins.
  3. Activated alpha subunit and beta-gamma subunits activate target proteins.
     • Alpha subunit hydrolyzes GTP to GDP, reassociates with beta-gamma subunits, turning off the signal.
• Potassium Channel Opening Example: Acetylcholine binds, beta-gamma subunits interact with the potassium channel, causing it to open and changing membrane potential.
• Secondary Messengers: GPCRs can produce secondary messengers like cyclic AMP, expanding the signal.
  • Epinephrine example: Activation of adenylyl cyclase which makes cyclic AMP, activating protein kinase A.

3. Enzyme-Coupled Receptors

• Transmembrane receptors that function as dimers.
• Signal molecule binding causes dimerization, activating the receptor.
• Generally involve enzymes.
• Receptor Tyrosine Kinases: Dimerization leads to phosphorylation of tyrosines, creating docking points for other proteins.
• Monomeric G protein (RAS) associates with receptor tyrosine kinases; when bound to GTP it is active.

Cyclic AMP and Gene Expression

• Activation of kinases leads to change in gene expression.
• Protein Kinase A needs to be translocated into the nucleus and phosphorylates the different transcription factors in the nucleus, causing changes in gene expression.

Phospholipids.

• Signal molecule binds to the G protein coupled receptor.
• Activated G protein can then phosphorylate or turn on phospholipase C.
• Phospholipase C can cut off the top of the phosphorylated inositol phospholipid which is a phospholipid that has phosphate groups on its head, releasing it inside the cell referred to as inositol one-four-five-triphosphate (IP3).
• There is also is a molecule leftover referred to diacylglycerol (two fatty acid tails and glycerol) left over in the membrane.

IP3 and Diacylglycerol

• IP3 travels into the cell, binds to an ion channel, releases calcium into the cytoplasm (stored usually always in ER).
• Calcium contributes more downstream effects.
• Calcium binds to phosphokinase C -> activates it.
• Phosphorylated phosphokinase and the calcium turn on the kinase that correlates other things.

Calcium As a Signaling Molecule

• Low in the cytoplasm, binds to calcium binding proteins(most common is calmodulin)
• Calcium released calmodulin or other calcium binding proteins. involved in signalling.
• Signal that it's interacting, when it's involved in signalling, calcium can interact once it's bound interact with with different kinases and turn those kinases on.

Enzyme Linked Receptors

• Enzyme linked receptors tend to occur in dimers.
• Dimers generally brought together with signal molecule
• Tyrosine kinases. when we have the two dimers brought together, they phosphorylate each other.
• They tend to phosphorylate on tyrosines (Kinase specificity).
• You'll have phosphorylated tyrosines that act are docking points in the cytosol