Biology I - Cell Biology Lectures 2025-2026 Study Notes

Instructor: Varvara Trachana, Associate Professor of Medical Biology, Cell Biology Director of the Laboratory of Biology.

Cell signaling involves various types of receptors that respond to specific external signals (ligands).

Definition: A continuous polypeptide chain that crosses the membrane seven times; consists of seven transmembrane α-helices.
- Examples of GPCRs include rhodopsin (in the eye), olfactory receptors (in the nose), and yeast mating receptors.
- They form a family of proteins that exist in bacteria for nutrient detection, but not associated with G-proteins.
- Largest family of receptors with hundreds of members, responding to hormones, neurotransmitters, and small signaling molecules.

Upon ligand binding, GPCRs undergo a conformational change enabling interaction with G-proteins located on the cytoplasmic side of the membrane.
G-proteins consist of three subunits: α, β, and γ, with α bound to GDP in resting state.
Ligand binding activates the G-protein, causing GDP to be released and GTP to bind, cleaving the protein into a GTP-bound α subunit and a βγ complex.
These components interact with membrane-localized targets to transmit signals.

The behavior of the α subunit determines the duration of G-protein activation.
The α subunit functions as a GTP hydrolase, hydrolyzing GTP back to GDP, which leads to termination of the signal.
Both α and βγ complexes can modulate target proteins.

Cholera Toxin:
- Caused by bacteria producing cholera toxin, which modifies the α subunit of G-proteins, inhibiting GTP hydrolysis.
- Continuous activation of the G-protein targets adenylyl cyclase, leading to excessive cAMP production.
- Result: Continuous outflow of Cl⁻ and water leading to severe diarrhea and dehydration.
Pertussis Toxin:
- Inactivates the Gi G-protein by preventing its activation.
- Causes various reactions such as the release of insulin, resulting in hypoglycemia.
- Exact mechanism for coughing is unclear.

Types of Targets: Can include ion channels or membrane enzymes leading to significant physiological changes (e.g., heart rate regulation).
K⁺ Channel Activation: G-proteins can regulate K⁺ channels, decreasing heart contraction frequency when acetylcholine binds to receptors.

Key Enzymes: Adenylate cyclase and phospholipase C.
Function of Adenylate Cyclase: Converts ATP to cyclic AMP (cAMP), a crucial second messenger.
Phospholipase C: Produces inositol 1,4,5-triphosphate (IP3) and diacylglycerol (DAG), both critical for further intracellular signaling pathways.

Mechanism: Active GPCRs stimulate adenylyl cyclase, indirectly causing rapid synthesis of cAMP.
Effects: Includes activation of protein kinase A (PKA), which phosphorylates various target proteins involved in metabolism, gene transcription, and cellular responses.
Rapid Effects: Such as phosphorylation of glycogen metabolism enzymes, and slower effects like gene expression modulation in endocrine cells.

This pathway enhances intracellular Ca²⁺ levels using signaling molecules activating phospholipase C, producing IP3 and DAG.
Function of IP3: Triggers Ca²⁺ release from the endoplasmic reticulum.
Roles of Ca²⁺: In muscle contraction, neurotransmitter release, and oocyte fertilization signaling.
Calcium-binding proteins (like calmodulin) activate specific kinases (CaM-kinases) essential for various cellular processes, including memory formation.

Light activation in photoreceptors involves rhodopsin activating transducin G-proteins, leading to membrane ion channel closure and subsequent signal transmission to the brain.

Function: Respond to local mediators triggering cell growth, differentiation, and survival; linked with cancer signaling.
Characteristics: Have a single transmembrane region and often act as tyrosine kinases.
Activation: Occurs through ligand-induced dimerization, leading to receptor autophosphorylation and recruitment of intracellular signaling proteins.

The activation involves phosphorylation cascades that transmit signals related to cell proliferation and survival.

Cells utilize a variety of signaling pathways, enabling complicated responses to stimuli through phosphorylation events and the convergence of signals from different pathways.
Understanding of these pathways is ongoing, emphasizing the intricate nature of cellular communications.

Cellular signaling mechanisms are vital for maintaining homeostasis, responding to environmental changes, and determining cell fate; with numerous implications in health and disease, particularly in cancer.