Cell Communication

Lecture 11: Chapter 11 - Cell Communication

Overview

  • External Signals

    • Local and Long-Distance Signals

    • Stages of Cell Signaling

  • Signal Reception

    • Plasma Membrane Receptors

    • Intracellular Receptors

  • Signal Transduction

    • Pathway Overview

    • Protein Phosphorylation and Dephosphorylation

    • Second Messengers

  • Cellular Response

    • Regulation

  • Apoptosis

    • Pathways

External Signals

Evolution of Cell Signaling

  • Bacterial Cell Signaling (1970s)

    • Critical among prokaryotes; bacteria secrete molecules that can be detected by other bacterial cells.

    • Monitors cell density vs. quorum sensing.

    • Coordinates behavior of all cells in a population.

      • Example: Biofilm

        • Communities of bacteria that attach to surfaces and form a protective film.

        • Requires a certain density of bacterial cells; aggregation occurs when bacteria secrete molecules and attach to a surface.

        • Protects bacterial cells while they live off nutrients provided by the surface.

        • Involved in approximately 80% of human bacterial infections (e.g., slimy coatings on fallen logs or leaves, film on teeth in the morning).

Types of Cell Signaling

  • Local Signaling

    • Signals travel short distances, targeting nearby cells.

      • Modes of Local Signaling:

        • Direct Contact

          • Via cell junctions connecting cells.

          • Examples include gap junctions in animal cells and plasmodesmata in plant cells.

          • Important in processes like embryonic development and immune response.

        • Paracrine Signaling

          • Signaling molecules secreted by one cell act on nearby cells.

          • Example: Growth factors, stimulate nearby cells to grow and divide.

        • Synaptic Signaling

          • Occurs in the animal nervous system; electrical signals travel along neurons.

          • Triggers release of neurotransmitters that diffuse across the synapse to act as chemical signals.

          • Relevant in pharmacology (e.g., antidepressants, anxiety medications, PTSD).

  • Long-Distance Signaling

    • Signals are transmitted through the bloodstream to target distant cells.

      • Example: Endocrine Signaling

        • Hormones act as signaling molecules; released into circulation and travel to their target cells.

        • Example: Insulin, released from the pancreas to regulate blood sugar levels.

Stages of Cell Signaling

  • Originating from Earl Sutherland's research in the 1970s.

    • Example Insight: Understanding how epinephrine triggers the sympathetic nervous system mobilizes fuel reserves for fight or flight responses by stimulating glycogen breakdown in the liver and skeletal muscle, liberating glucose for energy.

  • Key Steps in Cell Signaling:

    1. Signal Reception

      • A target cell detects a signaling molecule from outside by binding to a receptor.

    2. Signal Transduction

      • The binding converts the external signal into a cellular response, either through a single step or multiple steps (signal transduction pathway).

    3. Cellular Response

      • A specific cellular response is triggered (e.g., catalysis, cytoskeletal rearrangement, gene activation).

Signal Reception

  • Analogy for Signal Reception:

    • Like WIFI, which broadcasts signals; access depends on having the correct password (the receptor).

Mechanism of Signal Reception

  • A signaling molecule (ligand) binds to a receptor, causing a shape change.

  • Ligands are detected by various cells, but only cells with specific receptor proteins can respond.

  • Binding induces activation of the receptor protein.

Types of Signal Receptors

  • Plasma Membrane Proteins:

    • Primary type of signal receptors (around 30% of all human proteins).

    • G Protein-Coupled Receptors (GPCRs):

      • Largest family of plasma membrane receptors (about 800 types).

      • Example: Beta-2 adrenergic receptor - binds to epinephrine, Chemokine receptor 5 targets maraviroc for AIDS.

    • Intracellular Receptors:

      • Found in the cytoplasm or nucleus of target cells; regulate gene expression and cellular function.

Plasma Membrane Protein Receptors

  • Types:

    • G Protein-Coupled Receptors (GPCRs):

      • Use G proteins, which bind to GTP to activate.

      • Variants have different binding sites; activate a transduction pathway.

      • Structure: 7-transmembrane alpha helices.

      • Important in embryonic development and sensory reception (vision, smell, taste).

      • Bacterial toxins can interfere with G-protein function causing disease (cholera, whooping cough, botulism).

    • Receptor Tyrosine Kinases (RTKs):

      • Membrane receptors that transfer phosphate groups to tyrosine residues.

      • Can activate multiple pathways simultaneously, coordinating various cellular processes.

      • Abnormal RTKs are associated with many cancers (e.g., excess HER2 in breast cancer).

    • Ion Channel Receptors:

      • Ligand-gated channels that open or close as the receptor changes shape, regulating ion flow.

      • Critical for nervous system function;

      • Channelopathies are genetic mutations affecting channel function (epilepsy, tumor growth).

Signal Transduction

  • Pathway Overview:

    • Mechanism:

      1. Signaling molecule binds to a receptor.

      2. Activates a chain of molecular interactions.

      3. Results in a final cellular response.

    • Regulation:

      • Phosphorylation (addition of phosphate groups) and dephosphorylation (removal of phosphate groups) regulate protein activity.

      • Phosphorylation: Mediated by protein kinases, can create phosphorylation cascades.

      • Dephosphorylation: Conducted by protein phosphatases, can deactivate pathways.

Second Messengers

  • Examples of second messengers include small, nonprotein molecules like cyclic AMP (cAMP) and calcium ions (Ca²⁺).

  • cAMP Function:

    • Produced from ATP, carries signals from GPCRs.

    • Activates further signaling cascades resulting in cellular responses.

  • Cholera Toxin Example:

    • Contaminated water leading to constant cAMP stimulation, causing severe diarrhea and dehydration.

  • Calcium Ions:

    • Released by second messengers like inositol trisphosphate (IP3), regulate muscle contractions and cell divisions.

Cellular Response

Regulation of Cellular Response

  1. Signal Amplification:

    • Amplifies cellular responses through cascading effects in transduction pathways (e.g., epinephrine leads to the formation of many cAMP molecules).

  2. Signaling Specificity:

    • Signal response depends on the specific receptors present in target cells, leading to varied outcomes (e.g., liver vs. cardiac responses to epinephrine).

  3. Signaling Efficiency:

    • Scaffolding proteins enhance coordination and speed by organizing multiple relay proteins.

  4. Signal Termination:

    • Ensures short-lived signaling to avoid prolonged responses when ligands are scarce.

Apoptosis

  • Definition:

    • Programmed cell death, essential for normal development; senescence, infected, or damaged cells undergo this process.

  • Process:

    • Involves activation of caspases, which degrade cellular components leading to cell shrinkage and phagocytosis.

    • Protects neighboring cells from potential damages such as leaking harmful enzymes.

  • Clinical Relevance:

    • Abnormal apoptosis is linked to diseases.

    • Examples:

      • Alzheimer’s Disease associated with protein aggregation; excessive apoptosis leads to cognitive decline.

      • Melanoma linked to inadequate apoptosis resulting in uncontrolled cell division due to UV exposure.