Chapter 15: Signaling at the Cell Surface

Chapter 15: Signaling at the Cell Surface

Introduction to Signal Transduction

  • Focus on signaling within multicellular animals.

  • Signal transduction occurs when one cell type synthesizes a signaling molecule that initiates a specific response in a target cell.

  • Signaling molecules are referred to as ligands, and can be:

    • An amino acid (and derivatives)

    • Acetylcholine

    • A small peptide

    • A full protein

  • Target cells possess specific receptors for these extracellular ligands, which induce varied cellular responses including:

    • Cellular metabolism

    • Cell division (relevant in cancer)

    • Cell differentiation

    • Cell morphology or mobility

Overview of Signaling by Cell-Surface Receptors

  • Signaling Cell:

    • Produces and releases ligands (in relation to secretory pathways).

  • Responding Cell:

    • Cell surface receptors bind ligands, leading to a conformational change that activates a signal transduction cascade.

    • This often results in an elevation of "second messenger" levels and activation of effector proteins.

  • Responses typically include:

    • Cellular metabolism

    • Cell division

    • Cell differentiation

    • Cell structure or movement

Signaling Pathway Overview

  1. Inactive cell-surface receptor

  2. Signaling cell produces ligand.

  3. Responding cell binds ligand to activate receptor.

  4. Receptor becomes active, activating downstream signaling proteins.

  5. Effector proteins are activated, causing various cellular responses.

Signaling Molecules and Their Classification

  • Types of Signaling:

    • Endocrine Signaling:

    • Hormones secreted into the blood affecting distant target cells.

    • Example: Pancreas cells releasing insulin.

    • Paracrine Signaling:

    • Secretory cell affects nearby target cells.

    • Example: Neurotransmitter secretion by a nerve cell.

    • Autocrine Signaling:

    • Cells respond to signals they secrete themselves.

    • Often exhibited by cancer cells using growth factors.

    • Plasma-Membrane-Attached Proteins:

    • Proteins that cannot diffuse away from the source.

    • Example: Epidermal Growth Factor (EGF) mediating signals.

Ligands and Their Mechanisms

  • Definition of Ligands:

    • Small signaling molecules/proteins that bind to receptors on cell surfaces, inducing cellular responses.

    • Different receptors for the same ligand can trigger distinct responses.

  • Example of Ligand Responses:

    • Acetylcholine induces contractions in striated muscles (through ion channels) but has different effects in other cells (e.g., smooth heart muscle).

Types of Ligands: Hydrophilic vs. Lipophilic

  • Hydrophilic Ligands:

    • Cannot diffuse through the plasma membrane and include:

    1. Peptide hormones: Insulin, epidermal growth factor (EGF), and glucagon.

    2. Small Charged Molecules: Epinephrine, histamine, derived from amino acids.

  • Lipophilic Ligands:

    • Prostaglandins, which modulate hormone responses in paracrine and autocrine signaling, affecting inflammation and other functions.

  • Ligands interact via molecular complementarity, involving various types of interactions:

    • Hydrogen bonds

    • Ionic bonds

    • Van der Waals forces

    • Hydrophobic interactions

Second Messengers in Signal Transduction

  • Common Second Messengers include:

    • cAMP: Derived from ATP and activates protein kinase A (PKA).

    • cGMP: Activates protein kinase G (PKG).

    • DAG (Diacylglycerol) and IP3 (Inositol trisphosphate): Generated from phosphatidylinositol (PI) and lead to increased intracellular calcium levels.

  • The rise in second messengers influences:

    • Cellular proliferation

    • Glucose uptake

    • Fat mobilization

Protein Kinases and Signaling Pathways

  • Protein Kinases are crucial in signaling cascades, including:

    1. Tyrosine phosphorylation

    2. Serine/Threonine phosphorylation

  • Examples of kinases activated by signaling pathways include:

  • Phosphatases counteract these actions by removing phosphate groups.

G-Protein Coupled Receptors (GPCRs)

  • GPCRs comprise a significant family of receptors, roughly 800 types encoded in the human genome, including receptors for light, odorants, neurotransmitters, and hormones.

  • GPCRs are often targeted in pharmaceutical research due to their extensive physiological roles.

Conclusion

  • This chapter covers the complexity of signaling at the cell surface, how GPCRs function, and the myriad ways signals can influence cellular responses.

  • Details of downstream effects, second messengers, and specific signaling pathways are vital for understanding broader physiological processes and their implications in health and disease.

Notes on Future Chapters

  • Subsequent discussions will likely delve deeper into the molecular mechanisms of signaling pathways, feedback mechanisms, and pharmacological applications concerning GPCRs and their associated pathways.