Cell Communication

Essential Elements for Communication

• Signaling cells produce signaling molecules
• Receptor molecules, on receptor cells, bind to signaling molecules

Steps in Cell Signaling

• Receptor activation occurs when a signal binds to a receptor
• The signal is transmitted to the cell interior through a signal transduction pathway
• A cell responds by activating an enzyme or turning on gene transcription
• Termination of the response occurs so new signals can be received

Communication in Bacterial Cells

• Bacteria uptake DNA from the environment in response to signaling peptides
• At low cell density, the concentration of signaling peptide is too low to stimulate DNA uptake
• At high cell density, the signaling peptide concentration is high enough to stimulate DNA uptake

Signaling Over Long and Short Distances

• Endocrine signaling involves large distances
• Paracrine signaling reaches up to ~20 cells away
• Autocrine signaling occurs when a cell signals itself
• Juxtacrine signaling involves direct physical contact

Endocrine Signaling

• The signal travels through the circulatory system
• Adrenaline, released by adrenal glands, binds to receptors on heart cells and other organs, leading to a response

Growth Factors

• Growth factors stimulate cell growth
• Platelet proteins act as significant growth factors

Contact-Dependent Signaling

• Undifferentiated cells express the protein Delta
• Delta acts as the signal, and Notch acts as the receptor
• Delta expressing cells become neurons
• Notch expressing cells become glial cells

Signaling Molecule and Receptors

• A ligand is a signaling molecule
• A ligand-binding site is a location on the receptor where the ligand binds
• Ligand binding causes a conformational change in the receptor

Intracellular Receptors

• Nonpolar signaling molecules can cross the cell membrane
• They bind an intracellular receptor in the cytoplasm or nucleus

Cell-Surface Receptors

• Polar signaling molecules cannot cross the cell membrane
• They bind to transmembrane proteins, activating the receptor
• A conformation change occurs creating an activated receptor once bound

Cell-Surface Receptors

• There are typically thousands of different proteins on the surface of one given cell type
• The proteins involved in cell signaling can be classified into three main groups

Three Types of Cell-Surface Receptors

• G protein-coupled receptors
• Receptor kinases
• Ion channels

Two Types of Intracellular Receptors

• In the cytosol that interact with the nucleus
• In the nucleus

G Protein-Coupled Receptor

• A ligand binds to a receptor which activates a G protein

Receptor Kinase

• Binding of a ligand creates an active receptor kinase

Ligand-Gated Ion Channel

• The binding of a Ligand opens an ion channel

G Protein Activation

• Initially, the α subunit binds to GDP, and the three subunits are joined, making the G protein inactive
• When the G protein associates with an activated receptor
• GDP is replaced by GTP on the α subunit, separating it from the β and γ subunits
• The activated α subunit then binds to and activates a target protein

G Protein Activation Example

• Adrenaline activates adenylyl cyclase
• Activated adenylyl cyclase converts ATP into cAMP
• cAMP activates protein kinase A
• Activated protein kinase A phosphorylates proteins in the heart muscle, increasing heart rate

Amplification of Adrenaline Signal

• Each activated receptor activates multiple G proteins
• These, in turn, activate adenylyl cyclase enzymes
• Each adenylyl cyclase enzyme produces large amounts of cAMP
• cAMP activates a variety of protein kinase A molecules
• Each protein kinase A enzyme phosphorylates and activates proteins

G Protein Signal Termination

• Adrenaline detaches from the receptor when its concentration wanes, causing it to revert to an inactive form
• The receptor longer activates the G protein, causing GTP to convert to GDP
• As a result adenylyl cyclase no longer produces the second messenger cAMP

G Protein Signal Termination: The Role of Phosphatases

• Cytosol enzymes degrade cAMP preventing more protein kinase A activation
• Phosphatases remove phosphate groups from activated proteins rendering inactive

Fight-or-Flight Response

• Receptor activation leading to activation of G protein
• G protein activates adenylyl cyclase
• Adenylyl cyclase makes cAMP (2nd messenger).
• cAMP activates protein kinase A
• PKA activates GP kinase
• GP Kinase phosphorylates glycogen phosphorylase

Receptor Kinase Activation and Signaling

• Receptor kinase activation requires that each member of the receptor pair attaches phosphate groups to the other member
• The phosphate groups provide binding sites for intracellular signaling proteins

The MAP Kinase Pathway

• Platelet derived growth factor (PDGF) utilizes MAP Kinase Pathway

Ligand-Gated Ion Channel

• Acetylcholine binding opens ion channels, allowing Na+ to flow into the muscle cell

Cell Signaling and Cancer

• Cell signaling and cancer include:
  • Increased or altered receptors
  • Overproduced or altered signaling molecule
  • Ras mutations

Integration of Signaling Pathways

• Effects of integration can be:
  • Simple or complex
  • Different depending on cell type
  • Integrated