GS

Chapter 9 Cell Communication

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.