Cell Communication

Cell Communication

Overview of Cell Communication

  • Definition: The process by which cells communicate with each other to coordinate functions.

  • Importance: Essential for multicellular organisms to maintain homeostasis, respond to environmental changes, and regulate development.

Learning Objectives

  • Signaling Mechanisms: Describe four types of signaling mechanisms found in multicellular organisms.

  • Receptors: Compare internal receptors with cell-surface receptors.

  • Ligand Structure: Recognize the relationship between a ligand’s structure and its mechanism of action.

  • Signal Transduction: Explain how the binding of a ligand initiates signal transduction throughout a cell.

  • Phosphorylation: Recognize the role of phosphorylation in the transmission of intracellular signals.

  • Second Messengers: Evaluate the role of second messengers in signal transmission.

  • Apoptosis: Recognize the role of apoptosis in the development and maintenance of a healthy organism.

  • Yeast Signaling: Describe how single-celled yeasts use cell signaling to communicate with one another.

  • Quorum Sensing: Relate the role of quorum sensing to the ability of some bacteria to form biofilms.

Communication Terms

  • Intercellular: Communication between cells.

  • Intracellular: Communication within a cell.

  • Signaling Cells: Cells that send signals.

  • Ligand: A molecule that binds to a receptor.

  • Target Cells: Cells that receive signals from signaling cells.

  • Receptors: Proteins that bind ligands and initiate signaling pathways.

Forms of Signaling

  • Autocrine Signaling:

    • A cell targets itself, functioning in developmental roles and ensuring proper cell growth.

    • Example: Apoptosis or programmed cell death for regulating development.

  • Direct Signaling:

    • Involves gap junctions, connecting adjacent cells directly.

    • Facilitates coordinated responses between groups of cells (e.g., ions like Ca²⁺).

  • Paracrine Signaling:

    • Cells target nearby cells using ligands that degrade quickly to limit the signal range.

    • Example: Synaptic signaling, where neurotransmitters transmit signals across synapses (the gap between neurons).

  • Endocrine Signaling:

    • Hormones released into the bloodstream target cells far away from the signalling cell.

    • Characterized by slower but long-lasting responses.

    • Originates from various glands, including the pituitary, thyroid, adrenal glands, etc.

    • Example: Selection of hormones like insulin from the pancreas.

Receptors for Signaling

  • Internal Receptors:

    • Located within the cell, often regulating gene expression.

    • The receptor/ligand complex can enter the nucleus, binding to DNA, and promoting transcription.

  • Cell-Surface Receptors:

    • Transmembrane proteins anchored in cell membranes, specific to certain ligands.

    • Major components:

    • Extracellular domain: Binds the ligand outside the cell.

    • Transmembrane domain: Spans the membrane.

    • Intracellular domain: Initiates signaling cascades inside the cell.

Types of Cell-Surface Receptors

  • G-Protein Linked Receptors:

    • Activates a G-protein upon ligand binding.

    • Consists of 7 transmembrane domains; each has a specific binding site.

    • Mechanism:

    • Ligand binding induces a conformational change.

    • G-protein affinity shifts from GDP to GTP, activating the G-protein.

    • The alpha subunit dissociates to trigger cellular responses.

  • Enzyme-Linked Receptors:

    • Have an enzyme in their intracellular domain (e.g., kinase).

    • Large extracellular and intracellular domains, with a small membrane-spanning region.

Tyrosine Kinase Receptors

  • Function: Ligand binding induces dimerization of receptors, activating tyrosine kinase.

  • Phosphorylates tyrosine residues, acting as an intracellular signal to propagate responses.

Ligands and Their Mechanisms of Action

  • Types of Ligands:

    • Small Hydrophobic Ligands:

    • Diffuse through plasma membranes, interact with internal receptors.

    • Requires a protein to combine for transportation in blood.

    • Water Soluble Ligands:

    • Polar/hydrophilic, must bind to extracellular receptors to signal.

    • Example: Nitric Oxide (NO).

Signal Transduction

  • Definition: The process by which a cell converts an external signal into an internal response.

  • Mechanisms:

    • Requires cell-surface receptors; internal receptors can interact with DNA directly.

    • Dimerization: Two receptor molecules bind to form a functional complex, activating the receptor.

Signaling Pathways

  • Secondary Messengers: Small molecules propagate the signal within the cell (e.g., cyclic AMP, calcium ions).

  • Signal Integration: A single pathway can lead to multiple cellular responses, demonstrating intricate cellular signaling networks.

Intracellular Signaling: Phosphorylation and Dephosphorylation

  • Phosphorylation: The addition of a phosphate group (PO4³⁻) that can either activate or inactivate a target protein, mediated by kinases.

  • Dephosphorylation: The removal of phosphate groups, typically performed by phosphatases.

Second Messengers

  • Definition: Small molecules that carry signals originating from receptors to target proteins within the cell.

  • Examples:

    • Calcium ions (Ca²⁺)

    • Cyclic AMP (cAMP): Synthesized from ATP by adenylyl cyclase, activates cAMP-dependent protein kinase (A-Kinase).

    • Inositol Phospholipids:

    • Phosphatidylinositol (PI) is phosphorylated to form PIP2, which is cleaved by phospholipase C to produce DAG and IP3.

    • DAG activates protein kinase C (PKC), while IP3 diffuses within the cell to open calcium channels.

Response to Signaling

  • Inhibitors: Factors that can impair or block signaling response.

  • Growth Factors: Influence gene expression and cellular metabolism via signaling pathways (e.g., MAP Kinase and ERK).

  • Apoptosis: An essential biological process for development, maintaining tissue health and homeostasis.

Cell Signaling in Yeasts

  • Mating Factor:

    • Yeasts use mating factors that bind to surface receptors to initiate signaling cascades involving kinases and GTP binding proteins similar to G-proteins.

Bacterial Signaling: Quorum Sensing

  • Function: Enables bacteria to assess external conditions, nutrient availability, and ensure safety through collective signaling.

  • Autoinducers: Small hydrophobic and large peptide-based molecules used by cells to determine population density for signaling responses.

Overview of Cell Communication

  • Definition: Cells communicate to coordinate functions.

  • Importance: Crucial for multicellular organisms to maintain homeostasis, respond to environments, and regulate development.

Learning Objectives

  • Signaling Mechanisms: Describe four types of signaling mechanisms in multicellular organisms.

  • Receptors: Compare internal receptors with cell-surface receptors.

  • Ligand Structure: Relate ligand structure to its mechanism of action.

  • Signal Transduction: Explain how ligand binding initiates signal transduction.

  • Phosphorylation: Recognize the role of phosphorylation in intracellular signal transmission.

  • Second Messengers: Evaluate the role of second messengers in signal transmission.

  • Apoptosis: Recognize the role of apoptosis in organism development and maintenance.

  • Yeast Signaling: Describe how single-celled yeasts use cell signaling.

  • Quorum Sensing: Relate quorum sensing to bacterial biofilm formation.

Communication Terms

  • Intercellular: Between cells.

  • Intracellular: Within a cell.

  • Signaling Cells: Cells that send signals.

  • Ligand: A molecule that binds to a receptor.

  • Target Cells: Cells that receive signals.

  • Receptors: Proteins that bind ligands and start signaling pathways.

Forms of Signaling

  • Autocrine Signaling:

    • A cell targets itself. Important for development and cell growth (e.g., Apoptosis).

  • Direct Signaling:

    • Adjacent cells communicate directly through gap junctions (e.g., Ca^{2+} ions).

  • Paracrine Signaling:

    • Cells target nearby cells. Ligands degrade quickly to limit range.

    • Example: Synaptic signaling (neurotransmitters across synapses).

  • Endocrine Signaling:

    • Hormones released into the bloodstream target distant cells.

    • Characterized by slower, long-lasting responses.

    • Originates from glands (pituitary, thyroid, adrenal).

    • Example: Insulin from the pancreas.

Receptors for Signaling

  • Internal Receptors:

    • Located inside the cell (cytoplasm or nucleus), often regulate gene expression.

    • Ligand/receptor complex enters the nucleus, binds DNA, and promotes transcription.

  • Cell-Surface Receptors:

    • Transmembrane proteins anchored in the plasma membrane, specific to extracellular ligands.

    • Components:

      • Extracellular domain: Binds the ligand outside the cell.

      • Transmembrane domain: Spans the membrane.

      • Intracellular domain: Initiates signaling inside the cell.

Types of Cell-Surface Receptors

  • G-Protein Linked Receptors (GPCRs):

    • Activates a G-protein upon ligand binding.

    • Composed of 7 transmembrane domains, each with a specific binding site.

    • Mechanism:

      • Ligand binding causes conformational change.

      • G-protein exchanges GDP for GTP, activating it.

      • The alpha subunit dissociates to trigger cellular responses.

  • Enzyme-Linked Receptors:

    • Have an enzyme (e.g., kinase) in their intracellular domain.

    • Large extracellular and intracellular domains, small membrane-spanning region.

Tyrosine Kinase Receptors

  • Function: Ligand binding induces receptor dimerization, activating tyrosine kinase activity.

  • Phosphorylates tyrosine residues, which then act as intracellular signals to propagate responses.

Ligands and Their Mechanisms of Action

  • Types of Ligands:

    • Small Hydrophobic Ligands:

      • Diffuse through plasma membranes, interact with internal receptors.

      • Require transport proteins in the blood (e.g., steroid hormones).

    • Water Soluble Ligands:

      • Hydrophilic, must bind to extracellular cell-surface receptors.

      • Example: Nitric Oxide (NO).

Signal Transduction

  • Definition: The process of converting an external signal into an internal cellular response.

  • Mechanisms:

    • Primarily involves cell-surface receptors; internal receptors can interact directly with DNA.

    • Dimerization: Two receptor molecules bind to form a functional complex, activating the receptor.

Signaling Pathways

  • Secondary Messengers: Small molecules that amplify and propagate the signal within the cell (e.g., cyclic AMP, calcium ions).

  • Signal Integration: A single pathway can lead to multiple cellular responses.

Intracellular Signaling: Phosphorylation and Dephosphorylation

  • Phosphorylation: The addition of a phosphate group (PO_4^{3-}) to a protein by kinases, which can activate or inactivate it.

  • Dephosphorylation: The removal of phosphate groups from a protein by phosphatases.

Second Messengers

  • Definition: Small, non-protein molecules that relay signals from receptors to target proteins inside the cell.

  • Examples:

    • Calcium ions (Ca^{2+}): Involved in various cellular processes.

    • Cyclic AMP (cAMP):

      • Synthesized from ATP by adenylyl cyclase.

      • Activates cAMP-dependent protein kinase (A-Kinase).

    • Inositol Phospholipids:

      • Phosphatidylinositol (PI) is phosphorylated to form PIP_2.

      • PIP2 is cleaved by phospholipase C to produce DAG (Diacylglycerol) and IP3 (Inositol triphosphate).

      • DAG activates protein kinase C (PKC), while IP_3 diffuses to open calcium channels.

Response to Signaling

  • Inhibitors: Factors that can hinder or block signaling responses.

  • Growth Factors: Influence gene expression and cellular metabolism via signaling pathways (e.g., MAP Kinase and ERK).

  • Apoptosis: Programmed cell death; essential for development, tissue health, and homeostasis.

Cell Signaling in Yeasts

  • Mating Factor: Yeasts use mating factors that bind to surface receptors to initiate signaling cascades involving kinases and GTP binding proteins (similar to G-proteins).

Bacterial Signaling: Quorum Sensing

  • Function: Enables bacteria to assess external conditions, nutrient availability, and population density through collective signaling.

  • Autoinducers: Small hydrophobic and large peptide-based molecules used by cells to determine population density for signaling responses.