BSCI 1511 - Cell Signals and signal transduction

Cell Junctions

Gap junctions in animal cells and Plasmodesmata in plant cells. Channels between two cells allow molecules to directly pass from the cytoplasm of one cell to the cytoplasm of another, passing signals.

Direct contact

Cell to Cell contact

Receptor ligand interaction

Sender cells bind to the receptor cell

Paracrine signaling

Local signaling where cells release signals that affect nearby target cells.

Autocrine signaling

A type of signaling where cells respond to signals they produce themselves.

Synaptic signaling

Communication between nerve cells and their targets through neurotransmitter release across synapses.

Endocrine signaling

Hormonal signaling where molecules are released into the bloodstream to act on distant target cells.

Neuroendocrine signaling

A hybrid signaling where neurons release neurohormones into the blood to act on distant targets.

Signal Molecules (Cannot cross plasma membrane)

Hydrophilic molecules that bind to membrane receptors.

Signal Molecules (Can cross plasma membrane)

Hydrophobic molecules that pass through the cell membrane and bind to intracellular receptors.

G-protein-coupled Receptors (GPCRs)

Membrane receptors that activate intracellular signaling pathways upon ligand binding.

What are the 3 stages of cell signaling?

1. Signal reception

2. Signal transduction

3. Cellular response

How do GPCRs operate?

When a ligand binds to a GPCR, it is activated via a conformational change, which causes it to bind to a g-protein causing the GDP in the alpha subunit to be displaced by GTP, activating the g-protein

The activated alpha subunit dissociates from the other subunits and diffuses along the membrane till it binds to a specific enzyme, this enzyme becomes active, causing a cellular response

Alpha subunit of the g protein hydrolyzes GTP to GDP, inactivating itself and the enzyme. Then, the alpha subunit reassociates with the other subunits

Receptor tyrosine kinases (RTKs)

Enzyme-linked receptors that activate pathways by phosphorylation.

Ligand-gated Ion Channels

Channels that open in response to ligand binding, allowing ion flow also known as ionotropic receptors

Voltage-gated ion channel

Channels that open in response to changes in membrane potential, allowing ion flow

How do RTKs operate?

Ligand binds to receptor causing monomers to dimerize

Dimerization activates the tyrosine region of each monomer, which causes each tyrosine kinase to phosphorylate the tail of the partner monomer

An activated receptor is recognized by specific relay proteins in the cell, and binds to a phosphorylated tyrosine, which activates the protein inducing a signal transduction pathway leading to a cellular response

Signal Transduction

The process of converting an extracellular signal into a functional cellular response.

Advantages of signal transduction

• Amplification

• Tight regulation

• Additional pathways

Intracellular Receptors

Receptors inside the cell that bind to lipid-soluble signals.

RAS/MAP K Pathway

RAS is activated by exchanging GDP to GTP

The signal is passed to a series of protein kinases and the last kinase activates a transcription factor that turns one or more genes for a protein that stimulates the cell cycle

Second messengers

Water-soluble molecules that spread through the cell and activate a cellular response

Participates in pathways initiated by GPCRs and RTKs

Small and diffuse fast, easy to destroy or create

How does cAMP induce a cellular response?

Epinephrine binds to a GPCR, which activates a G protein, which activates adenyl cyclase which converts ATP to cAMP, and cAMP activates Protein Kinase A (PKA) by binding regulatory subunits, which release catalytic subunits. Activated PKA phosphorylates other proteins inducing cellular response

Use of cAMP in cholera

Cholera toxin binds to the receptor, causing the subunit to enter the cell and activate a g protein, which activates adenylyl cyclase

Adenyl cyclase catalyzes the uncontrollable production of cAMP, which activates protein kinases

The phosphorylation cascade leads to the secretion of chloride ions into the lumen of the intestine, causing a decrease in osmolarity, leading to diarrhea

Calcium as a second messenger

Involved in muscle contraction, secretion of molecules, and cell divsion

High concentration in the cytosol

What can cell signaling regulate?

Transcription, signaling pathways that may end with activation of transcription factors that turn genes on or off

The activity of proteins

How are signal transduction pathways regulated?

The many steps in a pathway provide control points for the cell’s response to be further regulated

Efficiency of the response is enhanced by scaffolding proteins

All signals must be terminated

How can the same signaling molecule induce different responses in different cells?

Different types of cells have different collections of proteins, which lead to different cellular events

What are Scaffolding proteins and what is the function?

Large relay proteins attach to other relay proteins

Increases speed and accuracy of signal transduction

Brings components closer and ensures the correct order

Ways to terminate a signal

Decreasing the concentration of the signal, hydrolyzing GTP to GDP, using protein phosphatase, internalizing receptors

IP3

A second messenger that is produced when phospholipase cleaves PIP 2

IP3 binds to a ligand-gated calcium channel, causing the release of calcium ions from the endoplasmic reticulum

What is phosphodiesterase and what does it do?

It regulates levels of cAMP by breaking down cAMP, which terminates the signal pathway

What is the pathway of epinephrine?

Epinephrine à GPCR à G Protein à Adenylyl cyclase à cAMP à Protein kinase A à Phosphorylase kinase à Glycogen phosphorylase à Glycogen is broken into glucose molecules that are released