Cell Communication and Receptor Families

Academic Credit

• Academic credit is available for this course.
• Blue flyers with information are available at the auditorium exit.

Introduction to Cell Communication

• Instructor: Karen Bodges, epilepsy researcher and teacher.
• Focus: Cell communication and receptor families.
• Engagement: Interactive sessions and workshops.
• Content and Resources:
  • Campbell Biology textbook.
  • Blackboard: Videos and materials.
  • Mastering Biology: Videos (also available on Blackboard).

Overview of Cell Communication Concepts

• Four main concepts will be covered:
  • External signals and their conversion into intracellular signals.

Modes of Cell Communication

• Cells perform varied functions (muscle contraction, immune response, nerve impulse transmission).
• Paracrine Signaling:
  • Cells secrete mediators (e.g., growth factors) via exocytosis.
  • Mediators diffuse and bind to receptors on target cells.
  • Examples: Interleukins, tumor necrosis factor, histamine (released by mast cells during allergies).
• Nervous System:
  • Electrical signals trigger neurotransmitter release.
  • Neurotransmitters diffuse across the synapse and act on receptors in the target cell.
  • Examples of neurotransmitters: Dopamine, serotonin, noradrenaline, acetylcholine, adrenaline.
• Long Distance Signaling:
  • Hormones and neurotransmitters are released into the bloodstream.
  • They travel to target organs to elicit effects.
  • Examples: Estrogen, testosterone, adrenaline.

Cell-to-Cell Communication Mechanism

• Signaling molecule binds to a receptor.
• Receptor transmits information via relay molecules.
• Transduction: Signal transduction within the cell, often involving second messengers.
• Response: Activation of a cellular function (e.g., enzyme activation for glycogen metabolism).

Types of Signaling Molecules

• Hydrophilic Signaling Molecules:
  • Stay in extracellular fluid or blood.
  • Bind to cell surface receptors.
  • Example: Adrenaline, acetylcholine.
• Hydrophobic Signaling Molecules:
  • Can pass through the cell membrane.
  • Bind to proteins in the cytoplasm.
  • Complex often moves to the nucleus to affect gene expression.
  • Example: Estrogen.

Key Terms

• Ligands: Molecules that bind to receptors (Greek for "binding").
• Agonists: Molecules that elicit a response.
• Antagonists: Molecules that block a response.

Receptor Types

• Four Main Receptor Types:
  • Ion Channel Linked Receptors (Ligand-Gated):
    • Ligand binding opens an ion channel.
    • Common for $Na^+$ channels.
    • Found in muscles (acetylcholine receptor) and the brain (glutamate receptor).
    • Fast signaling.
  • G Protein Coupled Receptors
    • Seven transmembrane spanning domains.
    • Involved in many physiological and pharmacological processes.
  • Tyrosine Kinase Linked Receptors
    • Examples: Insulin receptors, cytokine receptors.
    • Important in the immune system, metabolism, cell growth, and reproduction.
  • Steroid Receptors
    • Less emphasized in neuronal signaling.

Ligand-Gated Ion Channels

• Illustration: Acetylcholine binding to open a channel.
• Location: Postsynaptic neuron or skeletal muscle.
• Mechanism: Neurotransmitter binds, ions (e.g., $Na^+$) flow in, causing depolarization.
• Other Ion Channels:
  • Leaky ion channels (constitutively active).
  • Voltage-gated ion channels (open in response to voltage changes).

G Protein Coupled Receptors (GPCRs)

• Seven Transmembrane Domains (7 TMDs):
  • Caution: Spell out terms in exams; don't just use abbreviations.
• Diversity: Thousands of GPCRs in the genome.
• Orphans: ~150 GPCRs with unknown functions.
• Drug Targets: Over 50% of drugs target GPCRs.
• Activation:
  • By neurotransmitters or hormones (adrenaline, noradrenaline, dopamine, serotonin).
  • Peptides and proteins.
  • Light (rhodopsin).
  • Smell and taste molecules (olfactory neurons have one type of GPCR each; thousands exist).
• Heterotrimeric G Proteins:
  • Composed of alpha, beta, and gamma subunits.
  • Control enzymes, ion channels, and intracellular pathways when activated.
• Mechanism:
  • Signaling molecule binds to GPCR -> G protein activates -> Activation of adenylyl cyclase -> Production of cyclic AMP (cAMP) as a second messenger -> cAMP activates protein kinase A -> Cellular responses (muscle changes, enzyme release, etc.).
  • GTP (guanidine triphosphate) is involved; similar to ATP.
  • Amplification: One G protein leads to many cAMP molecules.
• Heterotrimeric Structure: G protein has alpha, beta, and gamma subunits.
• Activated G proteins act on enzymes (adenylyl cyclase, phospholipase, phosphodiesterase) or ion channels.
• Second Messengers:
  • cAMP (cyclic AMP).
  • cGMP (cyclic GMP, involved in vision).
  • Diacylglycerol (DIG) and Inositol Trisphosphate (IP3): Produced by phospholipase activity.
    • IP3 opens calcium channels in skeletal muscle leading to contraction.

Phosphorylation

• Addition of a phosphate group (PO4-) by kinases; removal by phosphatases.
• Receptor activation leads to phosphorylation cascades.
• Example: cAMP activates protein kinase A, altering glycogen metabolism.
• Mechanism:
  • Phosphorylation alters protein shape due to the negative charge of phosphate groups.
  • Shape change affects protein function (e.g., activating an inactive enzyme).
• Signal Transduction Time:
  • Altering glycogen metabolism takes time.
  • Neurotransmission requires speed, using direct ion channel opening.

Tyrosine Kinase Linked Receptors

• Function: Metabolism, cell growth, cell reproduction, immune system.
• Insulin:
  • Regulates blood glucose levels.
  • Diabetes: Occurs with insufficient insulin production.
• Mechanism:
  • Receptors dimerize upon ligand (e.g., insulin) binding.
  • Dimerization leads to phosphorylation of the cytoplasmic tail.
  • Phosphorylation attracts and activates other proteins in a signaling cascade.
• Insulin Example:
  • Insulin receptor is phosphorylated, attracts insulin receptor sensitive substrates.
  • Activation of kinases
  • Glucose transporters move to the membrane, facilitating glucose entry into muscle and fat cells.

Steroid Receptors

• Lipophilic Hormones: Estrogen, testosterone, aldosterone, cortisol.
• Mechanism:
  • Hormones pass through the cell membrane.
  • Proteins bind hormones in the aqueous environment.
  • Complex moves to the nucleus and alters gene expression (mRNA transcription).
  • Receptors are in the cytoplasm.