🔬General Biology I Unit 9 – Cell Communication

Key Concepts and Terminology

• Cell communication enables cells to respond to their environment and coordinate activities within tissues and organs
• Signaling molecules (ligands) bind to specific receptors on or within target cells
• Signal transduction pathways convert extracellular signals into intracellular responses
• Second messengers (cyclic AMP, calcium ions) amplify and propagate signals within cells
• Cellular responses to signals include changes in gene expression, metabolism, and cell behavior
• Regulation of signaling involves feedback loops, desensitization, and signal termination
• Malfunctions in cell signaling can lead to diseases (cancer, diabetes)

Types of Cell Signaling

• Autocrine signaling occurs when a cell responds to signaling molecules it has secreted itself
• Paracrine signaling involves local communication between cells in close proximity
  • Neurotransmitters and growth factors mediate paracrine signaling
• Endocrine signaling involves long-distance communication via hormones released into the bloodstream
  • Insulin and adrenaline are examples of hormones involved in endocrine signaling
• Juxtacrine signaling requires direct contact between signaling and target cells
  • Notch signaling pathway is an example of juxtacrine signaling

Signal Transduction Pathways

• Signal transduction pathways convert extracellular signals into intracellular responses
• Ligand binding to receptors triggers conformational changes that initiate signaling cascades
• G protein-coupled receptor (GPCR) pathways involve activation of G proteins and second messenger production
  • Cyclic AMP and calcium ions are common second messengers in GPCR pathways
• Receptor tyrosine kinase (RTK) pathways involve phosphorylation cascades and activation of transcription factors
  • Mitogen-activated protein kinase (MAPK) cascade is a well-studied RTK pathway
• Intracellular receptors (nuclear receptors) directly regulate gene expression upon ligand binding
  • Steroid hormones (estrogen, testosterone) act through intracellular receptors

Receptors and Ligands

• Receptors are proteins that specifically bind signaling molecules (ligands)
• Cell surface receptors include G protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs)
  • GPCRs have seven transmembrane domains and associate with G proteins
  • RTKs have an extracellular ligand-binding domain and an intracellular tyrosine kinase domain
• Intracellular receptors are located in the cytoplasm or nucleus and bind lipid-soluble ligands
  • Nuclear receptors directly regulate gene expression upon ligand binding
• Ligand binding induces conformational changes in receptors that initiate signaling cascades
• Ligand-receptor interactions are highly specific and determine the selectivity of cellular responses

Second Messengers and Signal Amplification

• Second messengers are small molecules that relay and amplify signals within cells
• Cyclic AMP (cAMP) is produced by adenylyl cyclase upon activation of G proteins
  • cAMP activates protein kinase A (PKA), which phosphorylates target proteins
• Calcium ions ($Ca^{2+}$) are released from the endoplasmic reticulum upon activation of phospholipase C
  • $Ca^{2+}$ binds to and activates calmodulin, which regulates various enzymes and ion channels
• Inositol trisphosphate ($IP_3$) is produced by phospholipase C and stimulates $Ca^{2+}$ release from the ER
• Diacylglycerol (DAG) is produced by phospholipase C and activates protein kinase C (PKC)
• Second messengers amplify signals by activating multiple downstream effector molecules

Cellular Responses to Signals

• Changes in gene expression lead to long-term alterations in cell behavior and function
  • Transcription factors (CREB, NF-κB) regulate the expression of specific genes in response to signals
• Modulation of enzyme activity affects cellular metabolism and energy production
  • Glycogen phosphorylase is activated by cAMP-dependent protein kinase (PKA) in response to glucagon
• Cytoskeletal rearrangements influence cell shape, motility, and adhesion
  • Rho GTPases regulate actin polymerization and cell migration in response to growth factors
• Regulation of ion channels controls membrane potential and electrical excitability
  • Voltage-gated calcium channels open in response to membrane depolarization

Regulation and Termination of Signaling

• Negative feedback loops prevent excessive signaling and maintain homeostasis
  • Inhibition of adenylyl cyclase by PKA limits cAMP production and signaling duration
• Receptor desensitization reduces responsiveness to persistent stimuli
  • Phosphorylation of GPCRs by G protein-coupled receptor kinases (GRKs) promotes receptor internalization
• Signal termination mechanisms remove signaling molecules and reset the system
  • Phosphodiesterases degrade cAMP, terminating its signaling effects
  • Calcium pumps and exchangers remove $Ca^{2+}$ from the cytoplasm, restoring basal levels
• Crosstalk between signaling pathways allows for integration and fine-tuning of cellular responses
  • Activation of PKC by DAG can modulate the activity of other signaling pathways

Real-World Applications and Examples

• Drugs targeting GPCRs (beta blockers, antihistamines) are used to treat various medical conditions
  • Beta blockers inhibit adrenaline signaling and are used to treat hypertension and heart disease
• Mutations in signaling proteins can lead to diseases such as cancer and developmental disorders
  • Activating mutations in Ras GTPase are found in many human cancers and promote uncontrolled cell growth
• Insulin signaling regulates glucose homeostasis, and its dysfunction contributes to diabetes
  • Insulin resistance in type 2 diabetes reduces the effectiveness of insulin signaling in target tissues
• Neurotransmitter signaling underlies communication between neurons in the nervous system
  • Dopamine signaling in the brain is involved in reward-seeking behavior and motivation
• Plant hormones (auxins, cytokinins) regulate growth, development, and responses to environmental stimuli
  • Auxins promote cell elongation and root formation in plants