Cell-cell communication: Types of receptors (2/24)

Overview of Cell Signaling

• Cells can respond differently to stimuli despite having similar receptors.

• The response is influenced by the specific intracellular cascade activated and the type of cell.

Receptor Structure and Function

• Receptors can look similar but activate different intracellular pathways.

• Example: Heart pacemaker cells vs. salivary gland cells:

  • Heart cells respond to acetylcholine with a change in firing rate.

  • Salivary gland cells secrete different substances in response.

• The same receptor type can have different cellular responses due to varying proteins expressed in different cell types.

G Protein-Coupled Receptors (GPCRs)

• GPCRs are a common class of receptors characterized by seven alpha-helices that span the membrane.

• When a ligand binds to the GPCR:

  • It triggers a conformational change, activating a G protein.

• G proteins are heterotrimeric (three different subunits - alpha, beta, gamma).

  • The alpha subunit binds GDP when inactive.

  • Activation causes GDP to be replaced by GTP, leading to further signaling.

Signal Transduction Process

• Ligand binding → Receptor activation → G protein activation → Effector protein activation.

• Example Effector: Adenylyl Cyclase (activated by Gs protein) converts ATP to cyclic AMP (cAMP), a second messenger.

cAMP and Protein Kinase A (PKA)

• cAMP activates PKA, which phosphorylates target proteins in the cell.

• Responses can vary based on the specific enzymes and proteins present in the cell, leading to diverse outcomes, such as:

  • Rapid responses (e.g., enzyme activation).

  • Longer-term changes (e.g., gene expression modifications).

Amplification of Signals

• A single ligand can activate multiple G proteins, leading to amplified cellular responses.

• Example responses include:

  • Quick release of glucose from liver cells during "fight or flight."

  • Changes in gene expression when signals require longer-term modifications.

Termination of Signaling

• To stop a response:

  • The reverse processes must occur.

  • G proteins hydrolyze GTP to GDP, returning to their inactive form.

  • Degradation of cAMP and dephosphorylation of proteins by phosphatases.

• Cells have built-in "turn off" mechanisms to prevent uncontrolled signaling.

Receptor Tyrosine Kinases (RTKs)

• RTKs dimerize upon ligand binding, activating their kinase activity to phosphorylate themselves (autophosphorylation).

• This creates docking sites for downstream signaling proteins.

MAP Kinase Pathway

• RTKs activate small G proteins (e.g., RAS).

• RAS toggles between GTP-bound (active) and GDP-bound (inactive) states, controlling downstream MAP kinase cascades.

• Activated kinases in this cascade can amplify signals and lead to responses like cell division and differentiation.

Summary of Cell Type Specific Responses

• Differences in responses due to:

  • Specific receptors present on cells.

  • Unique sets of proteins expressed in different cell types allowing for target specificity for kinases.

• Overall, signaling pathways are tightly regulated, with both amplification and termination mechanisms ensuring proper cell function.