BIO 221 FALL - CELL COMMUNICATION

What environmental conditions do cells respond to?

• Nutrients

• Temperature

• pH

• Osmotic conditions

• Light

• Oxygen availability

Why do cells need to communicate

Respond to environmental conditions and communicate with other cells

What type of communication do other cells result in

• Immune response

• Muscle contraction

• Sensing/Regulating cell density

• Nerve transmission

• Growth and development

• Injury response

What are the general themes of cell communication

1. Cell membrane

2. Extracellular signal

3. Activation of a signal transduction

4. Cellular response

5. Changing cell shape/movement

What does “Cell membrane receptor” mean

• Extracellular domain binds the signal

• causes conformational change in cytoplasmic domain

What does “Extracelular signal” mean

Signaling molecule

Environmental stimulus

What does “Activation of a signal transduction pathway” mean?

• Passing extracellular message to inside

  • Activation of series of proteins in sequence

What are cells covered in

Transmembrane proteins

Example of a response to changed conditions

Yeast cell responding to glucose

What is ‘Direct Intercellular Signaling’?

Signal passing through an intercellular channel from the cytosol of one cell to adjacent cells

What is an example of gap junctions

Connexons and Innexons

What is ‘Contact Dependent Signaling’

Membrane-bound signals bind to receptors on adjacent cells

Signal on membrane of one cell, receptor on other cell

What is a ‘Contact Dependent Signaling’ example

Immune system

What is ‘Autocrine Signaling’

Cells release signals that affect themselves and nearby target cells

What is an example of ‘Autocrine Signaling’

Also in immune system

What happens in ‘Autocrine Signaling’

Reduces signaling molecules, affects nearby cells and itself

What is ‘Paracrine Signaling’

Cells release signals that affect nearby target cells

What is ‘Endocrine Signaling’

Cells release signals that travel long distances to affect target cells

What is an example of “Endocrine Signaling’

Blood Stream

What is the first step of cell signaling

Receptor Activation

What happens during ‘Cell Signaling’

Binding of signaling molecule causes a conformational change in a receptor that activates its function

What is the second step of cell signaling

Signal Transduction

What happens during ‘Signal Transduction’

Activated receptor stimulates a series of proteins that forms a signal transduction pathway

What is the third step of cell signaling

Cellular Response

What happens during ‘Cellular Response’

Signal Transduction Pathway affects functions and or amounts of cellular proteins, producing a cellular response

What cellular response do enzymes cause

Altered metabolism, cell functions

What cellular response do structural proteins cause

Altered cell shape, movement

What cellular response do transcription factors cause

Altered gene expression, change types and amounts of proteins in the cell

Three basic types of cell surface receptors

1. Enzyme-Linked

2. G-Protein coupled

3. Ligand-gated

How do ‘Enzyme-Linked’ receptors function?

Binding of ligand (signaling molecule) activates catalytic domain of receptor

What acts as an enzyme in enzyme-linked cell surface receptors

The cytoplasmic domain

How does the cytoplasmic domain act as an enzyme in enzyme-linked cell surface receptors

When a signal comes through, the CD catalyzes a reaction

How do ‘G-Protein Coupled Receptors’ function?

Binding of ligand activates a G-protein

What is the function of g-protein coupled receptors similar to?

On/Off switches

What happens when GEF (bound by G_GDP) exchanges GTP for GDP

The inactive G_GDP becomes active as G_GTP

What happens when GEF (bound by G_GtP) exchanges GDP for GTP

The active G_GtP becomes inactive as G_GDP

What is the function of “Ligand-Gated Ion Channels”

Controls whether or not it is open by whether or not it is bound by a ligand

What happens when signaling molecules bind to the ligand-gated ion channel?

Ion channel opens and allows flow of ions through the membrane

How does a receptor that functions as a protein kinase work?

1. Signaling molecule binds and activates domain of receptor

2. Receptor can catalyze the transfer of a phosphate group (ATP) to protein

What is the first step in a GPCR reaction

A signaling molecule binds to a GPCR, causes GPCR to bind to G Protein

What is the second step in a GPCR reaction

G protein exchanges GDP for GTP.

G Protein dissociates from receptor and separates into an active alpha subunit and beta/gamma dimer

Activated subunits promote cellular responses

What are the activated subunits that promote cellular responses after a GPCR reaction

Alpha subunit and Beta/Gamma dimer

What is the third step of a GPCR reaction

Signaling molecule eventually dissociates from the receptor, alpha subunit hydrolyzes GTP into GDP+P

Alpha subunit and Beta/Gamma subunit dimmer reassociate

What is the first step in the example of ‘Intracellular (Nuclear) Receptors

Estrogen diffuses across the plasma membrane, enters the nucleus, binds to estrogen receptors

What happens to the receptors when the estrogen binds to them?

Receptors undergo conformational change

What is the second step in the example of ‘Intracellular (Nuclear) Receptors

Estrogen receptors form a dimer, bind next to specific genes, activate gene transcription

mRNAs then translated into proteins that affect the structure of the cell

What happens when a substrate undergoes phosphorylation?

ATP becomes ADP, substrate now has phosphate group attached

What happens when a substrate undergoes dephosphorylation

H₂O becomes a phosphate group

What enzyme is used in phosphorylation

Kinase

What enzyme is used in dephosphorylation

Phosphatase

How do you change the activity of a protein

Phosphorylation/Dephosphorylation

What is the first step in activating a signal transduction pathway with an enzyme-linked receptor

Receptor activation

What happens on the first step in activating a signal transduction pathway with an enzyme-linked receptor

Two EGF molecules bind to 2 EG receptor subunits, causes them to dimerize and phosphorylate each other

What happens when the 2 EGF molecules bind to the 2 EGF receptor subunits

They dimerize and phosphorylate each other

What is the second step in activating a signal transduction pathway with an enzyme-linked receptor

Relay between the receptor and protein kinase cascade

What is the third step in activating a signal transduction pathway with an enzyme-linked receptor

Protein kinase cascade

What is the fourth step in activating a signal transduction pathway with an enzyme-linked receptor

Activation of transcription factors

What is the fifth step in activating a signal transduction pathway with an enzyme-linked receptor

Cellular response

What happens on the second step in activating a signal transduction pathway with an enzyme-linked receptor

Relay protein binds to phosphorylated receptor and then to a second protein, stimulates a third relay protein (Ras), to release GDP and bind GTP

What stimulates the third relay protein?

The first relay protein binding to a phosphorylated receptor and then to a second protein

What happens when the third relay protein is stimulated

GDP is released and the protein binds GTP

What happens on the third step in activating a signal transduction pathway with an enzyme-linked receptor

Ras activates protein kinase 1, protein kinase cascade start

What happens in the protein kinase cascade?

PK (protein kinase) 1 phosphorylates PK2, PK2 phosphorylates PK3

What happens on the fourth step in activating a signal transduction pathway with an enzyme-linked receptor

PK 3 enters the nucleus and phosphorylates transcription factors

What happens on the fifth step in activating a signal transduction pathway with an enzyme-linked receptor

Transcription factors stimulate the transcription of specific genes

mRNAs are translated into proteins that cause the cell to progress through the cell cycle and divide

What can steps 2-4 of the activation of a signal transduction pathway with an enzyme-linked receptor be classified as?

Signal transduction

What is the activation of a signal transduction pathway with an enzyme-linked receptor in response to?

Damaged skin

What is Ras?

G-protein

What are second messengers?

Small molecules used to relay messages inside cells

What are second messengers commonly used in

Signal transduction pathways

What do second messengers do?

Amplify signals

What is an example of a second messenger?

cAMP

How is cAMP activated and formed?

Formed from ATP by adenylyl cyclase

How is cAMP inactivated

Phosphodiesterase converts cAMP to AMP by adding H₂O

What happens in the first step in activating a signal transduction pathway with a GPCR

Epinephrine binds, GPCR activated

G-protein binds to GTP —> alpha subunit dissociates from beta/gamma dimer

What happens in the second step in activating a signal transduction pathway with a GPCR

Alpha subunit binds to adenylyl cyclase

synthesis of cAMP from ATP

What happens in the third step in activating a signal transduction pathway with a GPCR

cAMP binds to the regulatory subunits of PKA —> catalytic subunits of PKA is release

What state is PKA in once PKA is released?

It is now active

What happens in the fourth step in activating a signal transduction pathway with a GPCR

Catalytic subunits of PKA use ATP to phosphorylate specific cellular proteins —> cellular response

What is ‘PKA’

Protein Kinase A

What can happen once PKA is activated?

Glycogen synthesis is inhibited or glycogen breakdown is stimulated

How is glycogen synthesis inhibited?

Glycogen Synthase (active) is ATP’d into Glycogen Synthase - P (inactive

How is glycogen breakdown stimulated

Phosphorylase Kinase (inactive) is ATP’d into Phosphorylase Kinase-P (active) 

Glycogen Phosphorylase (inactive) is ATP’d into Glycogen Phosphorylase-P (active)

What breaks down glycogen?

Glycogen phosphorylase

What happens when Glycogen Phosphorylase breaks down glycogen

Metabolize glucose —> Make energy!!