Cell Signalling and Communication

• Signalling coordinates cell function through cell-to-cell communication
• Information transmits from one cell to another, often over a distance, altering the receiving cell's behavior
• Molecular events in signalling pathways create a cascade to amplify signals and trigger cellular responses

Types of Signalling

• Endocrine signalling involves hormones secreted into the bloodstream acting on distant target cells
• Paracrine signalling acts on nearby target cells
• Autocrine signalling involves a cell releasing a signalling molecule that binds to its own receptors, changing its behavior
• Juxtacrine signalling uses direct contact between two cells

Signalling Molecules

• Signalling molecules include diverse substances like proteins, peptides, amino acids, nucleotides, steroids, fatty acids, and dissolved gases
• These molecules initiate a signalling cascade by binding to specific target cell receptors
• Hydrophobic molecules cross the plasma membrane to bind intracellular receptors, while hydrophilic molecules bind to cell-surface receptors

Receptors

• Receptors are proteins initiating cellular responses by binding to signalling molecules
• Cell-surface receptors are transmembrane proteins binding to hydrophilic signalling molecules outside the cell
• Intracellular receptors reside inside the cell, binding hydrophobic signalling molecules that cross the plasma membrane

Cell-Surface Receptors

• G protein-coupled receptors (GPCRs) activate intracellular G proteins to regulate enzymes and ion channels
• Receptor tyrosine kinases (RTKs) possess enzymatic activity, phosphorylating tyrosine residues upon ligand binding
• Ligand-gated ion channels open or close ion channels upon ligand binding, changing the cell's electrical potential through ion flow

Intracellular Receptors

• Intracellular receptors are located in the cytoplasm or nucleus and bind to hydrophobic signalling molecules that can cross the plasma membrane
• Ligand binding causes these receptors to act as transcription factors, regulating specific gene expression

Signalling Pathways

• Signalling pathways are molecular event series that occur post-receptor activation
• Protein modifications, like phosphorylation, often amplify and transmit the signal
• Common pathways: MAP kinase, PI3K/Akt, and JAK/STAT

Second Messengers

• Second messengers are small, intracellular molecules amplifying and spreading the signalling signal
• Common examples include cyclic AMP (cAMP), calcium ions (Ca2+), and inositol trisphosphate (IP3)

Regulation of Signalling

• Signalling pathways are highly regulated, ensuring appropriate response to external stimuli
• Regulation occurs at multiple levels, including receptor expression, protein modification, and feedback loops.
• Phosphatases halt pathways by removing phosphate groups from proteins
• GTPase activating proteins (GAPs) stimulate GTP hydrolysis by G proteins, inactivating them
• Feedback loops can amplify (positive) or dampen (negative) the signalling response

Significance of Signalling

• Signalling is vital for cell communication, development, and homeostasis
• It regulates growth, differentiation, movement, and apoptosis
• Signalling pathway defects can lead to diseases like cancer, diabetes, and neurological disorders