2.3 Cell signaling and communication

Cell signaling is the foundation of communication between cells in our bodies. It's like a cellular group chat where cells send and receive messages using chemicals. These messages tell cells what to do, from growing to dying, and keep our bodies running smoothly.

There are different types of signaling based on distance and receptor location. Cells can talk to themselves, their neighbors, or send messages across the body. Some messages are caught on the cell surface, while others sneak inside. Understanding these chats helps us grasp how our bodies work and what goes wrong in diseases.

Cell signaling pathways

Categories based on signaling distance

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• Cell signaling pathways are classified into three main categories based on the distance between the signaling and target cells
  • Autocrine signaling: a cell secretes a signaling molecule that binds to receptors on its own surface, triggering a self-response (growth factors)
  • Paracrine signaling: signaling molecules are released and diffuse locally to affect nearby target cells (neurotransmitters, local hormones)
  • Endocrine signaling: hormones are released into the bloodstream and travel long distances to reach target cells throughout the body (insulin, thyroid hormones)

Categories based on receptor location

• Cell signaling is also categorized based on the location of the receptors
  • Cell surface receptors: embedded in the plasma membrane and interact with extracellular signaling molecules (G protein-coupled receptors, receptor tyrosine kinases)
  • Intracellular receptors: located within the cytoplasm or nucleus and bind to signaling molecules that can pass through the cell membrane (steroid hormone receptors, thyroid hormone receptors)
• Gap junctions enable direct communication between the cytoplasms of adjacent cells, allowing rapid signal transmission (electrical synapses in neurons, cardiac muscle cells)

Receptors and ligands in signaling

Receptor-ligand interactions

• Receptors are proteins that specifically bind to signaling molecules called ligands, initiating a cellular response
• Ligands convey information between cells and can be hormones, neurotransmitters, growth factors, or other signaling molecules (epinephrine, serotonin, nerve growth factor)
• The binding of a ligand to its receptor induces a conformational change in the receptor, triggering downstream events that lead to a specific cellular response

Specificity and affinity of receptors

• Receptors exhibit specificity and affinity for their respective ligands, ensuring appropriate cellular responses to the correct signals
  • Specificity: the ability of a receptor to distinguish between different ligands and bind selectively to its target ligand (insulin receptor binds insulin, but not glucagon)
  • Affinity: the strength of the interaction between a receptor and its ligand; higher affinity indicates stronger binding (high-affinity receptors require lower ligand concentrations for activation)
• The concentration of ligands and the number of receptors on the cell surface modulate the intensity and duration of the cellular response (upregulation or downregulation of receptors can affect signal strength)

Signal transduction in cell communication

Signal transduction process

• Signal transduction converts an extracellular signal into an intracellular response
• The process involves a series of molecular events that amplify and propagate the signal from the receptor to effector molecules within the cell
• Signal transduction allows cells to respond to external stimuli by altering their behavior, gene expression, or metabolic activities (cell division, differentiation, apoptosis)

Specificity and regulation of signal transduction

• The specificity of signal transduction is achieved through specific receptor-ligand interactions and unique combinations of intracellular signaling molecules (different receptors activate distinct signaling pathways)
• Signal transduction pathways often involve the activation of protein kinases, which phosphorylate downstream target proteins, modulating their activity or location within the cell
• The duration and intensity of signal transduction can be regulated by various mechanisms
  • Receptor desensitization: prolonged exposure to a ligand can lead to reduced receptor sensitivity (G protein-coupled receptor internalization)
  • Feedback loops: downstream components of a signaling pathway can inhibit upstream components, limiting signal duration (negative feedback)
  • Phosphatases: enzymes that remove phosphate groups from signaling proteins, terminating their activity
• Dysregulation of signal transduction pathways can lead to various diseases (cancer, diabetes, autoimmune disorders)

Intracellular signaling cascades

Key components of signaling cascades

• Intracellular signaling cascades are series of sequential molecular events that transmit signals from the receptor to the final effector molecules within the cell
• Second messengers are small, diffusible molecules that relay signals from receptors to downstream effector proteins
  • Cyclic AMP (cAMP): generated by the activation of adenylyl cyclase; activates protein kinase A (PKA), which phosphorylates various target proteins
  • Calcium ions (Ca2+): released from the endoplasmic reticulum or enters the cell through ion channels; activates calcium-dependent proteins, such as calmodulin and protein kinase C (PKC)
  • Inositol trisphosphate (IP3): generated by the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2); triggers the release of Ca2+ from the endoplasmic reticulum
• Protein kinases transfer phosphate groups from ATP to specific amino acid residues (serine, threonine, or tyrosine) on target proteins, modulating their activity or interactions (MAP kinases, Akt kinase)
• Phosphatases remove phosphate groups from proteins, reversing the effects of protein kinases and providing a means to terminate or regulate signaling cascades (protein phosphatase 1, protein tyrosine phosphatases)

Scaffolding and gene regulation in signaling cascades

• Scaffold proteins are molecular platforms that bring together multiple components of a signaling pathway, facilitating their interaction and increasing the efficiency of signal transduction (Ras-binding proteins, A-kinase anchoring proteins)
• Transcription factors are proteins that regulate gene expression in response to intracellular signals by binding to specific DNA sequences and promoting or repressing the transcription of target genes (CREB, NF-κB, STAT proteins)