IB Bio Cell Signaling

A ligand is a

chemical that binds to another specific molecule

Signaling systems have evolved repeatedly, leading to a …

wide range of chemical substances being used as signaling molecules

What happens when a ligand binds to a receptor?

The ligand binds to a receptor, which causes a series of responses within a cell

Hormone: Types of Molecules, Mechanism of Transport, Distance Signal Travels, Duration of Signal, Effect on Target Cell

Types of Molecules: amines, peptides, or steroids

Mechanism of Transport: exocytosis into bloodstream

Distance Signal Travels: sending and receiving cells can be far apart

Duration of Signal: can persist for hours after secretion

Effect on Target Cell: alter gene expression, metabolism, shape, movement

Neurotransmitter: Types of Molecules, Mechanism of Transport, Distance Signal Travels, Duration of Signal, Effect on Target Cell

Types of Molecules: amines, gasses, amino acids, or esters

Mechanism of Transport: diffusion across synaptic gap

Distance Signal Travels: very short distance between adjacent neurons

Duration of Signal: quick: after secretion neurotransmitters are rapidly removed from the synaptic gap

Effect on Target Cell: excite or inhibit nerve impulses

Cytokines: Types of Molecules, Mechanism of Transport, Distance Signal Travels, Duration of Signal, Effect on Target Cell

Types of Molecules: small proteins

Mechanism of Transport: diffusion

Distance Signal Travels: sending and receiving cells can be near or far apart

Duration of Signal: quick: can persist for minutes after secretion

Effect on Target Cell: alter gene expression

Calcium Ion: Types of Molecules, Mechanism of Transport, Distance Signal Travels, Duration of Signal, Effect on Target Cell

Types of Molecules: ion

Mechanism of Transport: active pumping or facilitated diffusion

Distance Signal Travels: within a single cell

Duration of Signal: quick: very rapid

Effect on Target Cell: contraction or exocytosis

What molecules are hormones?

• Amines, peptides, proteins, glycoproteins, and steroid

What molecules are neurotransmitters?

• Amines, amino acids, peptides, esters, gases

Amines: Hormone

• small molecules synthesized by modification of amino acids

• melatonin - regulates circadian rhythm

Peptides: Hormone

• short polypeptide chain

• oxytocin that stimulates contraction of the uterus

Proteins: Hormone

• Larger polypeptide chain

• Insulin is secreted to lowers blood glucose levels

Glycoproteins: Hormone

• protein with a carbohydrate group attached

• Stimulate menstrual cycle

Steroid: Hormone

• Hormones are lipids derived from cholesterol and thus are similar to it

• Released from the ovaries and placenta to prepare the lining of the uterus for implantation of the fertilizer egg

Amino Acid: Neurotransmitter

• main inhibitory and excitatory messengers in the nervous system

• glutamic acid, and excitatory neurotransmitter that will activate post synaptic cells

Amines: Neurotransmitter

• small molecules synthesized by modification of amino acid

• serotonin which regulates mood

Peptides: Neurotransmitter

• chemical messengers made up of small chains of amino acids

• endorphins which alleviate pain

Esters: Neurotransmitter

• alcohol bonds to an acid

• acetylcholine which forms when acetic acid binds with choline

Gasses: Neurotransmitters

• gas molecules

• nitric oxide relaxed smooth muscles causing vasodilation

Binding of Ligands to Receptors

• Ligands and receptors are three-dimensional molecules with distinct shapes

• Atoms in the ligand will form chemical bonds with atoms in the receptor at a region called the binding site

• The shape of the ligand is complementary to the shape of the binding site, ensuring that each receptor will only bind to ligands of a particular structure

• The ability of the binding site of a receptor to bind specific ligands is called “specificity”. The fewer ligands a protein can bind, the greater its specificity

• Binding of the ligand to the receptor causes the shape of the receptor to change, which in turn stimulates a response in the cell

• The signaling ligand is released, unchanged

Specificity

The ability of the binding site of a receptor to bind specific ligands is called “specificity”. The fewer ligands a protein can bind, the greater its specificity

Hydrophilic signaling molecules

cannot cross the membrane lipid bilayer. These signaling molecules must bind to specific transmembrane receptors embedded in the plasma membrane.

Hydrophobic signaling molecules

Small hydrophobic signaling molecules, can cross the membrane lipid bilayer. These signaling molecules bind to receptors found on the inside of the cell, typically in the cytoplasm or nucleus.

The receptors have hydrophilic amino acids arranged on their surface so they can remain dissolved in aqueous fluids

Three Signaling Pathway Steps:

1. Reception: The process by which a cell detects a signal in the environment

2. Transduction: The process of activating a charge within a cell

3. Response: The change that occurs in the cell as a result of the signal

Response:

• The signaling molecules are called first messengers. They are extracellular factors, often hormones or neurotransmitters, that bind to specific receptors

• The signaling molecule binds to its receptor, which causes a change in the shape of the receptor.

Transduction:

• Transduction means “to convert into another form”

• Transduction happens when the binding of signaling molecule to the receptor induces a change in the shape of the receptor

What are the 4 general ways an activated receptors?

• Intracellular receptors that directly alter gene transcription

• Transmembrane proteins that are ligand-gated ion channels and allow specific ions to flow into or out of the cells

• Transmembrane receptors that activate GTP binding proteins

• Transmembrane receptors with enzymatic activity

Signaling cascades are…

a series of metabolic reactions in which one reaction triggers the next, in a linear fashion

Oftentimes a signaling cascade requires small molecules within the cell to act as intracellular messengers. The intracellular signaling molecules released by the cell in response to extracellular signaling molecules are called second messengers. Common second messengers include cAMP, nitric oxide and calcium ions

Signaling cascades are only necessary for hydrophilic ligands that must bind transmembrane receptors because they cannot cross the plasma membrane

Responses:

• changes in gene expression

• changes in cell metabolism

• changes in cell shape or movement

Structure of G-protein-coupled receptors (GPCRs)

• All GPCRs consist of a single polypeptide that is folded into a globular shape and embedded in a cell’s plasma membrane

• Seven segment of this molecule span the entire width of the membrane with portions that loop both inside and outside the cell

• The intracellular loops attach to a protein complex called a G-protein. There are many different G-proteins, all of which share a characteristic structure; they are composed of 3 subunits (alpha, beta, and gamma)

G-protein Components

• composed of 3 subunits (alpha, beta, and gamma)

How to tell a GPCR is inactive

A molecule called GDP is bound to the alpha subunit of the G-protein complex and the entire G protein complex is attached to a nearby GPCR.

G-Protein Coupled Receptor activation occurs when:

1. A ligand binds to the G-protein-coupled receptor, causing the receptor to change shape

2. The shape changes causes the GDP to detach from the alpha subunit of the G-protein

3. GTP binds in its place

4. Binding of GTP causes the G protein subunits to dissociate into two parts: the GTP bounded alpha subunit and a beta-gamma subunit

5. Both parts remain anchored to the plasma membrane, but they are no longer bounded to the GPCR, so they can now diffuse laterally to interact with other membrane proteins

What are some signaling ligands that bind to G-protein-coupled receptors?

• Odor molecules and pheromones

• Taste molecules

• Hormones

• Neurotransmitters

• Different medicines

Epinephrine

• Also known as adrenaline

• Amine hormone produced by the adrenal glands in the kidneys

The reaction produced by epinephrine is known as:

• the “fight or flight” response. It evolved as a survival mechanism, enabling mammals to quickly react to retreat from threat.

• It evolved as a survival mechanism, enabling mammals to quickly react to retreat from threat

Effects of Epinephrine:

• Causes the liver and muscle cells to break down glycogen into glucose

• Bronchi and bronchioles dilate due to relaxation of the smooth muscles, widening the airway for increased airflow during ventilation

• Ventilation rate increases

• Speeds up the firing of the SA node to increase the heart rate

• Increases the strength of cardiac contraction

• Arterioles that carry blood to the skeletal muscles dilate, widening so more blood flows to them and vasoconstriction to other areas of the body

Why is the receptor for epinephrine located on the cell membrane?

This is because epinephrine is hydrophilic and cannot pass through the hydrophobic center of the plasma membrane of cells; therefore, the epinephrine receptor is found on the surface of target cells

Circadian rhythm are…

the physiological and behavioral changes of an organism over a roughly 24-hour cycle. They dictate many processes including alertness, appetite.

Circadian rhythms are known to exist in…

• unicellular cyanobacteria

• protozoans

• all multicellular organisms

In mammals, what is the pacemaker of the circadian rhythm?

it is the superchiasmatic nucleus. Neurons in the SCN produce a circadian rhythm of neuron firing frequency allowing the cells to synchronize in the body.

Visible light synchronizes the rhythm of…

of the superchiasmatic nucleus to the day-night cycle. Cells in the eye sense wavelength of light and send a neural impulse to the superchiasmatic nucleus.

• Light: SCN inhibits secretion of melatonin form the pineal gland

• Dark: SCN promotes secretion of melatonin from the pineal gland

The amount of melatonin circulating in the blood is…

low during the day and high at night

G-Coupled Protein Reaction for epinephrine

1. A ligand binds to the G-protein-coupled receptor, causing the receptor to change shape

2. The shape changes causes the GDP to detach from the alpha subunit of the G-protein

3. GTP binds in its place

4. Binding of GTP causes the G protein subunits to dissociate into two parts: the GTP bounded alpha subunit and a beta-gamma subunit

5. Both parts remain anchored to the plasma membrane, but they are no longer bounded to the GPCR, so they can now diffuse laterally to interact with other membrane proteins

6. The activate alpha subunit of the G-protein activates an enzyme in the cell membrane called adenylate cyclase

7. Enzymes are molecules that catalyze metabolic reactions in cells. The activate adenylyl cyclase the conversion of ATP in the cytoplasm to cyclic AMP

8. cAMP is a second messenger in a signal cascade. cAMP is able to rapidly diffuse through the cytoplasm

9. cAMP activates other molecules which in turn propagate the epinephrine signal into many different physiological changes in the cell

G-Coupled Protein Reaction for Melatonin

1. A ligand binds to the G-protein-coupled receptor, causing the receptor to change shape

2. The shape changes causes the GDP to detach from the alpha subunit of the G-protein

3. GTP binds in its place

4. Binding of GTP causes the G protein subunits to dissociate into two parts: the GTP bounded alpha subunit and a beta-gamma subunit

5. Both parts remain anchored to the plasma membrane, but they are no longer bounded to the GPCR, so they can now diffuse laterally to interact with other membrane proteins

6. The activated alpha subunit of the G-protein inhibits an enzyme in the cell called adenylate cyclase

7. The inhibited adenylate cyclase cannot catalyze the conversion of ATP into cAMP

8. Activation of the melatonin receptor will inhibit the formation of cAMP, reducing cell activity

Why is the receptor for melatonin located on the cell membrane?

This is because melatonin is hydrophilic and cannot pass through the hydrophobic center of the plasma membrane of cells; therefore, the melatonin receptor is found on the surface of target cells.

How does melatonin integrate the whole body response to the day-night rhythm?

• reduces blood pressure

• reduce kidney production of urine

• drop core body temperature when sleeping

• enhance the helper T immune response and reduce inflammation

• alter blood flow to different body tissues

Insulin receptor activation occurs when:

1. Insulin binds to the receptor

2. The binding of insulin causes the structure of the receptor to change, so the two tails connect

3. Tyrosine kinase in the tail of the receptor phosphorylates

Insulin signal transduction occurs when:

4. The phosphorylated tyrosine kinases then launch a series of metabolic reactions in the cell

Insulin response occurs when:

5. One of the results of the insulin signaling cascade is the movement of vesicles embedded with glucose-transport (GLUT) proteins to the plasma membrane

6. When the vesicles fuse with the plasma membrane, the transport protein becomes part of the plasma membrane

7. The glucose - transporter is a channel protein through which glucose enters the cell by facilitated diffusion. Once in the cell, the glucose can be use in cellular respiration or stored as glycogen

Insulin is a protein hormone secreted by the pancreas when…

blood glucose levels are high

Insulin is used to integrate the response of multiple organs in an effort to…

maintain blood glucose levels

Insulin causes cells to uptake glucose from the blood to be:

• used in cellular respiration

• converted to glycogen

What is glycogen?

It is a polysaccharide made of glucose monomers that is used for long term energy storage

Where is the insulin receptor and why?

Insulin is hydrophobic and cannot pass through the hydrophobic center of the plasma membranes of cells; therefore, the insulin receptor is found on the plasma membrane

Insulin binds to cells with…

a type of transmembrane receptor called a Receptor Tyrosine Kinase (RTK)

Phosphorylation is the…

attachment of a phosphate group to a molecule

Tyrosine kinase enzyme phosphorylates

A tyrosine kinase enzyme phosphorylates (adds a phosphate group to) certain proteins with a tyrosine amino acid. The enzyme gets the phosphate group from ATP and gives it to the protein.