Cell Communication

Module 1: Cells

UNIT 4: Cell Communication

Overview

  • Key Reference: Campbell Biology, Urry, Cain, Wasserman et al., Third Canadian Edition

  • Chapter Reference: Chapter 11

Definitions

  • Signalling Molecule (First Messenger): A molecule that initiates cellular communication by binding to a receptor.

  • G Protein: A membrane protein that binds to GTP or GDP and plays a critical role in signal transduction.

  • Cytosol: The liquid found inside cells in which organelles are suspended.

  • G Protein-Coupled Receptor (GPCR): A large family of receptors that work with G proteins to transmit signals inside the cell.

  • Phospholipase C: An enzyme that plays a role in the signaling pathway.

  • PIP (Phosphatidylinositol 4,5-bisphosphate): A phospholipid that is a substrate for phospholipase C.

  • Endoplasmic Reticulum (ER): An organelle involved in the synthesis of proteins and lipids.

  • IP3 (Inositol Triphosphate): A molecule that is produced by the action of phospholipase C and acts as a second messenger.

  • DAG (Diacylglycerol): Another product of phospholipase C that serves as a second messenger.

  • Cellular Responses: Activities initiated inside a cell following the activation of a receptor and the subsequent signaling pathway.

Cellular Communication

General Principles

  • Cells communicate via chemical signals that can be interpreted and converted into internal responses.

  • This communication is vital for cell function and coordination among cells.

Example: Fight-or-Flight Response

  • Triggered by the signaling molecule Epinephrine (Adrenaline).

  • Initiates physiological changes preparing the body for rapid response.

Types of Signaling

Local Signaling

  • Cell Junctions: Allow for direct passing of signaling molecules between adjacent cells (e.g. gap junctions).

  • Cell-Cell Recognition: Direct contact signaling in animals.

  • Local Regulators: Chemicals that only travel short distances. - Examples:

    • Paracrine Signaling: Growth hormones affecting nearby cells.

    • Synaptic Signaling: Neurotransmitters released from neurons.

Long-Distance Signaling

  • Hormones: Chemical messengers that travel long distances through the circulatory system.

  • Known as Endocrine Signaling in animals.

Overview of Cell Signaling

  1. Reception: The target cell detects a signaling molecule bound to its surface receptor.

  2. Transduction: The signal triggers a series of biochemical steps inside the cell.

  3. Response: The transduced signal eventually triggers a specific response in the target cell.

Reception

  • The binding of a signaling molecule (ligand) to a receptor is specific, causing a conformational change in the receptor that initiates transduction.

Cell-Surface Transmembrane Receptors

  • Hydrophilic signal molecules bind to cell-surface receptor proteins.

  • Types of Receptors:

    1. G Protein-Coupled Receptors (GPCRs): Largest family; act with G proteins.

    2. Receptor Tyrosine Kinases (RTKs): Attach phosphates to tyrosines, triggering multiple pathways.

    3. Ion Channel Receptors: Ligand-gated channels that allow ions to pass through the membrane.

G Protein-Coupled Receptors (GPCRs)

  • Family Characteristics: Also called guanine nucleotide-binding proteins and serpentine receptors.

  • Molecular Switch:

    • OFF State: GDP is bound, making G protein inactive.

    • ON State: GTP is bound, activating the G protein.

G Protein Structure

  • Composed of three subunits: Alpha (α), Beta (β), and Gamma (γ).

How Epinephrine Works

  • Activates enzymes involved in glycogen metabolism:

    • Activates Phosphorylase Kinase

    • Activates Glycogen Phosphorylase

    • Leads to glycogen breakdown into glucose.

Receptor Tyrosine Kinases (RTKs)

  • Function: Membrane receptors that phosphorylate tyrosines.

  • Can trigger multiple signal transduction pathways at once.

  • Abnormal Function: Linked to various cancers due to mutational dysregulation.

  • Mechanism:

    • Ligand binding causes RTKs to dimerize and autophosphorylate.

    • RTKs phosphorylate themselves on tyrosines.

  • Example: HER2 receptor related to some breast cancers.

Ion Channels

  • Ligand-Gated Ion Channel Receptors: Change shape upon ligand binding, allowing permeability for specific ions such as Na⁺ or Ca²⁺.

Intracellular Receptors

  • Found in cytosol or nucleus; respond to small or hydrophobic chemical messengers that cross the plasma membrane.

  • Examples: Steroids and thyroid hormones.

  • Mechanism:

    • HSPs (Heat Shock Proteins) trap messenger inside the cell.

    • Hormone-receptor complexes can act as transcription factors.

Second Messengers

  • Ligands as first messengers initiate signaling.

  • Second Messengers: Small molecules that diffuse inside the cell, e.g., cyclic AMP (cAMP) and calcium ions (Ca²⁺).

  • Function of cAMP in Dysfunction: E.g., cholera toxin modifies G protein to remain active, leading to excessive salt secretion in intestinal cells.

Calcium Ions (Ca²⁺)

  • Serve as a crucial second messenger; their concentration is tightly regulated.

  • Signal transduction pathways can trigger calcium influx, activating calcium-dependent enzymes.

DAG and IP3

  • Pathways that release Ca²⁺ involve two additional second messengers:

    • DAG (Diacylglycerol)

    • IP3 (Inositol Triphosphate)

Nuclear and Cytoplasmic Responses

  • Many signaling pathways influence gene regulation by turning genes on/off.

  • Final activated molecule may act as a transcription factor influencing gene expression.

Regulation of the Response

  • Responses can be fine-tuned with four major aspects:

    1. Amplification of the signal.

    2. Specificity of the response.

    3. Efficiency enhanced by scaffolding proteins (linked to the cytoskeleton).

    4. Termination of the signal.

Signal Amplification

  • Enzyme cascades increase the number of activated products exponentially with each step, leading to significant cellular responses.

Specificity of Signaling and Coordination

  • Different cells contain unique collections of proteins, allowing varying responses to the same signals due to pathway branching and "cross-talk".

Termination of the Signal

  • Inactivation Mechanisms: Critical for proper signal termination; decrease in ligand concentration leads to fewer receptor bindings.

  • Unbound receptors revert to an inactive state, completing the signaling cycle.