Animal Anat/Phys -- Cell Signaling

Cell Signaling

Communication between cells, can be direct or indirect.

Direct Cell Signaling

Signaling cell and target cell connected by gap junctions. Signal is passed directly from one cell to another through these channels.

Indirect Cell Signaling

Signaling cell releases a chemical messenger which is carried in the extracellular fluid. Messenger binds to a receptor on the target cell, activating the signal transduction pathway and needs a response in the target cell.

Short Distance Signaling

Can be either paracrine or autocrine.

Paracrine Signaling

Short distance; chemical messenger diffuses to a nearby cell

Autocrine Signaling

Short Distance; Chemical message diffuses back tot he same cell that produced it.

Mast Cells

Have both autocrine and paracrine responses; release histamines

Long Distance Signaling

The Endocrine or Nervous System

Endocrine System

Long Distance Signaling; Chemical messenger (hormone) transported by the circulatory system

Nervous System

Long Distance Signaling; Electrical signal travels along a neuron and a chemical messenger (neurotransmitter) is released.

Chemical Messengers

Peptides, Steroids, Amines, Lipids, Purines, and Gases

Steroids

Derived from cholesterol, synthesized by smooth ER or mitochondria. Hydrophobic and therefore must be synthesized on demand. Can pass through plasma membranes but cannot be stored in the cell. Bind to intracellular or transmembrane receptors. Slowing effect on target cells. Have 3 classes.

Mineralocorticoids

Steroids; Electrolyte Balance

Glucocorticoids

Steroids; Stress Hormones

Reproductive Hormones

Steroids; Regulate sex-specific characteristics

Peptides/Protein Hormones

2-200 amino acids long; synthesized on the rough ER and often as larger prehormones, stored in vesicles (prohormones) and secreted by exocytosis.

Amines

Chemicals that possess an amine (NH2) group; Hydrophilic

Eicosanoids

Lipids; Most act as paracrines, hydrophibic, often involved in pain and inflammation

Purines

Function as neuromodulators and paracrines

Gases

Most act as paracrines

Receptors on the Target Cell

Hydrophilic messengers bind to transmembrane/intracellular receptors

Ligand

Chemical messenger that can bind to a specific receptor. May bind to more than one receptor (different isoforms)

Natural Ligand

Chemical messenger correctly shaped to bind to the receptor

Ligand Mimics

Agonist, Antagonists

Agonists

Ligand Mimic; Activate Receptors

Antagonists

Ligand Mimic; Block Receptors

If L>R

R becomes saturated by large amounts of L

More Receptors =

More L-R complexes; more response

Up-Regulation

Target cell increases the number of receptors by building them with rough ER, begins exocytosis for binding.

Down-Regulation

Target cells decrease the number of receptors, likely due to high conc. of ligands

Ligand Removed by Distant Tissue

Ligand detaches from the receptor and enters the circulatory system where it can be degraded by the liver or kidneys.

Ligand taken up by Adjacent Cell

Ligand detaches from the receptor and is absorbed by another cell; endocytosis into another cell (Non-polar bond).

Ligand Degraded by Extracellular Enzymes

Ligand detaches from the receptor and is degraded by extracellular enzymes.

L-R Complexes removed by Exocytosis

L-R complex undergoes endocytosis into its own cell where it degrades, enters vesicles and is degraded by intracellular enzymes

Receptor Inactivation

L-R complex undergoes phosphorylation on the R side of the complex, thereby inactivating the complex.

Inactivation of Signal Transduction Pathway

Intracellular inactivated signaling protein disrupts the signaling pathway of the L-R complex, making it unable to communicate.

Signal Transduction Pathway

Convert the change in receptor shape to an intracellular response. Four components include receiver, transducer, ampliffier, and responder.

Receiver

Signal Transduction Pathway Component; Ligand binding region of the receptor.

Transducer

Signal Transduction Pathway Component; Conformational change of the receptor, changes shape and acclimation

Amplifier

Signal Transduction Pathway Component; Increase number of molecules affected by signal.

Responder

Signal Transduction Pathway Component; Molecular functions that change in response to a signal.

Unbound ligand-gated ion channel

Without the ligand attached to the ligand-binding site, the ion channel is closed, and therefore no ions can pass through the membrane into the cell.

Bound ligand-gated ion channel

When the ligand is bound to the ligand-binding site, the ion channel opens and allows the flow of ions into the cell.

Receptor Enzyme

A receptor that once activated begins to act as an enzyme

G-Protein-Coupled Receptor; Step 1

Ligand binds to a G-Protein-Coupled receptor causing a conformational change.

G-Protein-Coupled Receptor; Step 2

The activated receptor signals to an associated G protein, causing the alpha subunit to release GDP and bind GTP.

G-Protein-Coupled Receptor; Step 3

The activated alpha or beta-y subunits move through the membrane and interact with an amplifier enzyme.

G-Protein-Coupled Receptor; Step 4

The activated amplifier enzyme converts and inactive second messenger into its active form.

G-Protein-Coupled Receptor; Step 5

The activated second messenger actiavtes or inhibits cellular pathways.

Intracellular Receptor: Step 1

Hydrophobic ligands pass through the cell membrane

Intracellular Receptor: Step 2

Inside the cell, the ligand binds to the L-R domain of the intracellular receptors.

Intracellular Receptor: Step 3

Ligand binding changes the shape of the receptor

Intracellular Receptor: Step 4

The receptor-ligand complex translocated to the nucleus

Intracellular Receptor: Step 5

The DNA-binding domain of the receptor binds to responsible element DNA sequences, and the transactivating domain interacts with other transcription factors bound in this region.

Intracellular Receptor: Step 6

together, these transcription factors alter the rate of transcription of the target genes into mRNA.