9.1 Signaling Molecules and Cellular Receptors

Learning Objectives

• Describe four types of signaling mechanisms found in multicellular organisms

• Compare internal receptors with cell-surface receptors

• Recognize the relationship between a ligand’s structure and its mechanism of action

Four Categories of Signaling

A ligand is a molecule that brings a signal to a cell and initiates a response.

1. Autocrine Signaling

   • Signaling cells bind to the ligand they released; signal and target cells can be the same or similar (e.g., cell death signaling).

2. Direct Signaling Across Gap Junctions

   • Intracellular mediators allow small signaling molecules to pass between cells directly.

3. Paracrine Signaling

   • Signals diffuse through the extracellular matrix; examples include synaptic signals and neurotransmitters.

4. Endocrine Signaling

   • Signals from distant cells, producing slower and long-lasting effects (e.g., hormones).

Example of Paracrine Signaling: Synapse Between Nerve Cells

• The close distance between presynaptic and postsynaptic cells allows for rapid diffusion of neurotransmitters.

• Enzymes in the synaptic cleft degrade neurotransmitters to terminate the signal.

Cell-Surface Receptors

• Types include ion channel-linked receptors, G-protein-linked receptors, and enzyme-linked receptors.

Ion Channel-Linked Receptor

• Form a pore in the plasma membrane; opens when a signaling molecule binds, allowing ions to flow in/out of the cell.

G-Protein-Linked Receptor

• When a signaling molecule binds, the G protein's alpha subunit exchanges GDP for GTP; this activates a cellular response as GTP is hydrolyzed back to GDP.

Enzyme-Linked Receptor

1. Receptor tyrosine kinases have transmembrane regions and extracellular/intracellular domains.

2. Binding of a signaling molecule leads to receptor dimerization.

3. Tyrosine residues are autophosphorylated, triggering downstream responses.

4. Termination involves phosphatases that remove phosphates from proteins.

Internal Receptors

• Hydrophobic signaling molecules diffuse across the plasma membrane to interact with intracellular receptors.

• Many of these receptors are transcription factors regulating gene expression.

Signaling Molecules

• Small hydrophobic ligands: Steroid hormones resemble cholesterol and diffuse across membranes.

• Water-soluble ligands: Typically bind to cell-surface receptors.

• Gas ligands: Example is nitric oxide.

9.2 Propagation of the Signal

Learning Objectives

• Explain how ligand binding initiates signal transduction throughout a cell.

• Recognize phosphorylation's role in intracellular signal transmission.

• Evaluate the role of second messengers in signal transmission.

Signal Transduction Mechanism

• Signal transduction: Process initiated when a ligand binds to a receptor, transmitting the signal across the membrane into the cytoplasm.

• Dimerization: Two receptors bind, forming a stable complex.

• Signaling pathway: A sequence of events including second messengers, enzymes, and activated proteins post-ligand binding.

• Signal integration: Merging signals from multiple cell-surface receptors to activate the same cellular response.

Example of a Signaling Pathway: EGFR

• The epidermal growth factor receptor (EGFR) regulates cell growth, wound healing, and tissue repair.

• EGF binding to EGFR sets off a downstream cascade resulting in cell growth/division; inappropriate activation could lead to cancer.

Second Messengers

• Example: Formation of cyclic AMP (cAMP) serves as a second messenger to activate/inactivate proteins within the cell.

• Signal termination occurs via phosphodiesterase, converting cAMP to AMP.

9.3 Response to the Signal

Learning Objectives

• Describe how signaling pathways influence protein expression, cellular metabolism, and cell growth.

• Recognize apoptosis's role in maintaining a healthy organism.

Gene Expression and Cell Signaling

• ERK: A MAP kinase that activates translation upon phosphorylation; phosphorylates MNK1, which in turn phosphorylates eIF-4E, facilitating mRNA unfoldment for protein synthesis.

Responses to Cell Signaling

• The same signal can yield different cellular responses, including:

  • Increased cellular metabolism: e.g., adrenaline activating β-adrenergic receptors, which increases cAMP and activates PKA.

  • Cell growth: Growth factors binding to tyrosine kinases initiate a pathway involving RAS and MAP kinase, promoting cell division.

Programmed Cell Death: Apoptosis

• Example: In the developing mouse embryo, apoptosis eliminates unnecessary tissue between toes before gestational completion.

• Signal termination occurs through ligand degradation or through phosphatases that remove phosphate groups from proteins.

9.4 Signaling in Single-Celled Organisms

Learning Objectives

• Describe how single-celled yeasts use signaling to communicate.

• Relate quorum sensing in bacteria to biofilm formation.

Signaling in Yeasts

• Yeast cells communicate via the signaling molecule called mating factor.

• Mating factor binds to surface receptors, halting growth cycles and initiating a signaling cascade.

Signaling in Bacteria

• Bacterial signaling relies on population density, termed quorum sensing, that requires a sufficient cell number to activate signaling.

• Involves molecules called autoinducers.