Lecture 3-12: General Principles of Cell Signaling

General Principles of Cell Signaling

Overview of Cell Communication

• Cells communicate using chemical signals.

• Signaling is essential for processes such as growth, immune responses, and homeostasis.

Signal Transduction

• Definition: The conversion of information into different forms.

• Involves extracellular signals being translated into intracellular responses.

• Diagram: Shows extracellular signal, target cell, and intracellular signaling molecules.

Types of Cell Signaling

Distance-Based Signaling

• Paracrine Signaling:

  • Release of soluble signals into the local environment.

  • Any cell with a matching receptor will respond.

• Autocrine Signaling:

  • The cell releasing the signal also has a receptor for it.

• Neuronal (Synaptic) Signaling:

  • Involves specific signaling in a narrow space (synapse) between neurons.

• Contact-Dependent Signaling:

  • Requires physical contact between signaling and target cells (membrane-bound receptors).

• Endocrine Signaling:

  • Hormonal signals travel long distances through the bloodstream to act on distant cells.

Signal Molecules and Their Actions

Examples of Signal Molecules

• Hormones:

  • Derived from amino acids or cholesterol; exert various effects.

  • Examples:

    • Epinephrine: Increases metabolism, heart rate, and blood pressure.

    • Insulin: Stimulates glucose uptake, laying a metabolic foundation in tissues.

• Local Mediators:

  • Epidermal Growth Factor (EGF): Stimulates cell proliferation.

  • Histamine: Causes blood vessels to dilate, leading to inflammation.

Receptor Dynamics

Receptor Classification

• Cell Surface Receptors:

  • Located on the plasma membrane; accommodate polar/charged signal molecules.

  • Activate intracellular signaling cascades.

• Intracellular Receptors:

  • Found inside the cell; respond to hydrophobic signaling molecules that can diffuse through the membrane.

  • Often act as transcription factors to alter gene expression.

Single Signal, Multiple Effects

• Acetylcholine:

  • Polar neurotransmitter affecting various cells differently.

  • Heart Pacemaker Cells: Decrease action potential generation.

  • Salivary Gland Cells: Induce secretion.

  • Muscle Cells: Activates an ion channel leading to contraction.

Integration and Modulation of Signals

Signal Integration

• Response to multiple signals can lead to varied cellular effects.

• Example: Signals A, B, C promote cell survival; signals D, E encourage division.

• Absence of all signals leads to apoptosis, showcasing the importance of survival signals.

• Anoikis: Form of apoptosis due to loss of adhesion to the extracellular matrix.

Dual Responses to Signals

Fast vs. Slow Responses

• Fast Effects:

  • Occur in seconds to minutes; alter protein function and cell behavior.

• Slow Effects:

  • Take minutes to hours; involve altered protein synthesis.

Pathway Complexity

Branching and Convergence of Signaling Pathways

• Pathways often involve branches that produce different outcomes based on the combination of signals.

• Example: A signal can activate pathways that lead to growth, division, or differentiation, depending on the cellular context.

Feedback Mechanisms in Signaling

• Positive Feedback: Stimulates upstream factor to increase activity.

• Negative Feedback: Inhibits upstream factor activity, stabilizing the signal response.

Molecular Switches in Signaling

Phosphorylation and GTP Binding

• Phosphorylation:

  • Managed by protein kinases and phosphatases to toggle signals on/off.

• GTP Binding Proteins:

  • Function as molecular switches; controls are mediated by GTP and GDP binding.

General Receptor Types

1. Ion-Channel-Coupled Receptors

• Open or close in response to ligand binding, affecting membrane potential directly.

2. G Protein-Coupled Receptors (GPCRs)

• Associated with inactive G protein complexes; ligand binding activates signaling branches.

3. Enzyme-Coupled Receptors

• Often have intrinsic catalytic domains active upon ligand-induced dimerization.

Effects of Foreign Substances

Substances Acting on Cell-Surface Receptors

• Barbiturates/Benzodiazepines: Stimulate GABA receptors, providing sedative effects.

• Nicotine: Stimulates acetylcholine receptors, affecting nerve signaling.

• Morphine/Heroin: Act on opiate receptors for pain relief.

• Curare: Blocks acetylcholine receptors, leading to paralysis.

Key Concepts

• Signal Transduction: Transformation of messages; typically converts extracellular stimuli to cellular responses.

• Distance and Interaction: Classify signaling based on distance covered and number of responding cells.

• Integration and Complexity: Different signals can combine for diverse responses; pathways amplify, branch, and cross-communicate.

• G Proteins: Governed by GTP binding; essential for the relay of signals.

• Receptor Varieties: Include ion-channel, G-protein coupled, and enzyme-coupled receptors, with distinct functional roles.