BIOMG 1350 - Lecture 15

Cell Signaling I

General Principles of Signaling Pathways

Signal binds to receptor which causes a series of intracellular events that go to effectors which leads to a cellular response.

Additional Signals Besides Signaling

• Light and mechanical forces

  • When your eye dilates when it’s dark

  • Venus fly trap, trapping anything that lands on the leaves.

Some Signals Can Act Over Long Distances.

• Endocrine Signals

  • Hormones

• Synaptic

  • Neurons

Endocrine Signals Step 1

Signal is secreted into the blood stream

Endocrine Signals Step 2

Allows the signal to travel throughout the body.

Endocrine Signals Step 3

Signal can reach any target cell that have a receptor for that signal.

Synaptic (Neurons) Step 1

Pass an electrical signal down the axon

Synaptic (Neurons) Step 2

Causes a release of neurotransmitters at the end of the cell

Synaptic (Neurons) Step 3

Neurotransmitters are received by the target cell (muscle, nerve or other cell)

Some Signals Can Travel In Short Distances.

• Paracrine

• Contact-dependent (shortest range)

Paracrine Signaling Step 1

A cell secretes a signal into the extracellular environment

Paracrine Signaling Step 2

This signal is received by its neighbors

Paracrine

Are also known as “local mediators” and include histamine, nitric oxide, and growth factors.

Contact-dependent Signaling Step 1

A membrane-bound signal binds to a membrane bound receptor on an adjacent cell.

Signals Can Act Fast Step 1

Extracellular signal molecule binds to a receptor protein.

Signals Can Act Fast Step 2

The result of this signaling is immediately altered protein function.

Signals Can Act Fast (<sec to min)

This means proteins that were already present in the cell are being turned on or off or are changing their function.

• Ex. Adrenalin (epinephrine) Fight or Flight Mode

Signals Can Act Slowly Step

Signal causes a change in gene expression

Signals Can Act Slowly (mins to hrs)

This means remodeling the chromatin, transcribe the gene, translate the gene, maybe modify protein or send it to a different place in the cell.

• Longer Lasting effects

One Signal (rate)

Can have both fast or slow effects

One Signal (responses)

Can induce different responses in different target cell

Heart Pacemaker Cell

Decreased Rate of Firing

Salivary Gland Cell

Secretion of Saliva

Skeletal Muscle Cell

Contraction of the Muscle

Ways One Signal Can Cause different Effects

• Having different receptors

• Different Proteins passing cell and carrying out response

Receptors

Can be intracellular or cell-surface receptors

Steroid Hormones

Regulate Transcription

• Are small enough to diffuse into the cell membrane to reach intracellular receptor.

Intracellular Receptors

Signaling Molecule needs to be small enough to diffuse into the cell membrane

• small and hydrophobic

Signal Transduction

The processes of translating an extracellular signal into intracellular effectors that alter cell behavior.

Intracellular Signaling Pathway

Relay, amplify, integrate, distribute

Effector(s)

May alter: gene expression, metabolism, cytoskeleton etc.

Response

May include: Cell division, growth, survival, migration, secretion, contraction, and differentiation

Functions of Intracellular Signaling Pathways

There can be many different molecules involved

• Adaptors, kinases, phosphates, GTP binding proteins, proteases, other enzymes, lipids (PIP2), 2nd messengers (cGMP, cAMP, Ca++)

Second Messengers

Are small molecules or ions that can be produced in large quantities which quickly amplify and spread a signal.

Feedback

Can Fine tune response (turn it up or down)

• Often proteins that can activate or represses other proteins

Molecules that provide feedback

Kinases, Phosphates, GTP-binding proteins

Many Key Intra Cellular Signaling Proteins act as molecular switches

• Signaling by protein phosphorylation

• Signaling by GTP-Binding Proteins

Positive Feedback

Occurs when a downstream component of a pathway activates an upstream component of the pathway.

• X → Y (positive feedback) X→YYYY

• All or none response (mCDK)

Negative Feedback

A downstream of protein inhibits or inactivates an upstream protein in pathway

• Turns down or turns off response

• X→Y (negative feedback) X→ nothing

→

Indicate activation

-|

Indicates repression/inactivation

Intracellular Signaling Pathways Integrate

Proteins Integrates information from other signaling pathways to effectors

• Can lead to better coordination of the effectors

Cells need a signal to live

Signal integration and feedback decide life or death

Regulation of cell signaling also occurs outside the cell

A signal can be destroyed, activated or Sequestered )held by proteins or sugar outside of the cell (signal jail) or blocked from its receptor.

A Receptor can be (membrane)

Added or removed from the membrane. Can be destroyed in lysosome. Or turned on/off

Receptor Blocking Example

A protein Lefty prevents Nodal from binding to receptor.

Organization of internal organs

Across the left-right body axis depends on both positive and negative feedback.

Correct Organization Step 1

Nodal is secreted proteins that signals “this is the left side"

Correct Organization Step 2

Positive Feedback of Nodal to itself ensures lots of the “this is left” signal is present on the left side.

Correct Organization Step 3

Negative Feedback of Nodal by Lefty ensures that the right side doesn’t receive any of the “this is left” signa;

What if we do a lose-it experiment for Lefty expression

Left isomerism - there will be two left sides

Cell-cell communication in animal development

is mediated by only a small number of conserved signaling pathways