Cell Communication & Homeostasis

Communication, Integration, and Homeostasis

• Future advancements in medicine hinge on the ability to quantitatively understand interconnected molecular networks in cells and tissues.

Cell-to-Cell Communication

• Physiological signals are broadly classified into electrical, involving changes in a cell's membrane potential, and chemical, where molecules are secreted into the extracellular fluid.
• Target cells respond to signals via receptor proteins and the binding of chemical signals follows specificity, affinity, competition, and saturation principles.
• Local communication involves gap junctions, contact-dependent signals, and paracrine/autocrine signals; long-distance communication utilizes nerve cells and blood-transported chemical signals.
• Gap junctions facilitate direct electrical and chemical signal transfer through protein channels (connexons) between adjacent cells, creating cytoplasmic bridges. These channels can be modulated or shut off, allowing for selective passage of ions and small molecules.
• Contact-dependent signaling involves surface molecules on one cell binding to membrane proteins of another, crucial in the immune system and during growth and development
• Paracrine signals affect cells in the immediate vicinity, while autocrine signals act on the signaling cell itself.
• The nervous system communicates using a combination of electrical and chemical signals, where electrical signals are converted to chemical signals at the neuron's end.
• Neurocrine molecules include neurotransmitters for rapid, localized effects; neuromodulators for slower, autocrine/paracrine actions; and neurohormones for body-wide distribution via the bloodstream.
• Cytokines, regulatory peptides for immune responses, can function as autocrine, paracrine, or long-distance signals.

Signal Pathways

• Signal pathways involve a signal molecule (ligand) binding to a receptor, activating it, which then affects intracellular signals and leads to the cell initiating a response by modifying existing proteins or creating new ones.
• Lipophilic signal molecules diffuse into cells and bind to cytosolic or nuclear receptors, often impacting gene activity; lipophobic molecules bind to cell membrane receptors, leading to rapid responses.
• Membrane receptors can be receptor-channels, G protein-coupled receptors, receptor-enzymes, or integrin receptors; all utilize signal transduction to transmit information across the membrane.
• Signal transduction involves extracellular signals activating membrane receptors that then alter intracellular molecules in a cascade.

Signal Amplification

• In signal transduction pathways, the original signal is both transformed and amplified, turning one signal molecule into multiple second messenger molecules.
• Signal transduction involves an extracellular signal molecule binding to and activating a membrane receptor
• Activated membrane receptors turn on associated proteins and starts an intracellular cascade of second messengers.
• Last cascade messenger acts on intracellular targets to create a response.

Receptor Types and Signalling

• Receptor channels function by ligand binding opening or closing the channel, altering ion flow.
• G protein-coupled receptors (GPCRs) activate G proteins upon ligand binding, leading to changes in ion channel activity or enzyme activity, and the activation requires guanosine triphosphate (GTP).
• G protein-coupled receptors are linked to adenylyl cyclase, which converts ATP to cyclic AMP (cAMP); and protein kinases are activated by cAMP.
• Some G protein-coupled receptors are linked to phospholipase C (PLC), which generates diacylglycerol and inositol trisphosphate that causes calcium release.
• Receptor-enzymes have extracellular receptor regions and intracellular enzyme regions to facilitate ligand activated intracellular activity.
• Integrin receptors mediate blood clotting, wound repair, cell adhesion, and recognition in the immune response, and cell movement during development.

Novel Signal Molecules

• Calcium functions as a versatile intracellular messenger, entering cells through ion channels or being released from internal stores (Ca2+ sparks).

Gasses as Signalling Molecules

• Gases such as nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S) act are potent for short periods of time, acting close to their creation site.
• Nitric oxide acts as a neurotransmitter and neuromodulator in the brain
• Nitric Oxide (NO) is synthesized by nitric oxide syntase on the amino acid arginine

Lipids as Signalling Molecules

• Eicosanoids, derived from arachidonic acid, act as paracrine signals via G protein-coupled receptors: leukotrienes play roles in asthma and anaphylaxis; prostanoids (prostaglandins and thromboxanes) affect various tissues and are targeted by NSAIDs.

Signal Pathway Modulation

• Responses depends on a cell's receptors and include:
  • Receptors exhibiting specificity, competition, and saturation
  • Agonists which activate
  • Antagonists which block
  • The presence or absence of isoforms
  • Cellular modulation via down/up regulation.

Responses and Adaptations

• Cells can vary their responses by modifying receptors (down-regulation, desensitization, up-regulation) to maintain normal activity levels.
• Cells terminate signals by:
  • Extracellular enzyme activity
  • Transport into neighboring cells
  • Endocytosis/exocytosis.

Homeostatic Reflex Pathways

• Cannon's postulates described the nervous system regulating internal environment "fitness", tonic control, antagonistic control, and varied chemical signal effects in different tissues.
• Feedback loops use reflex pathways with input, integration, and output components.
• Long-distance pathways integrates the nervous system, the endocrine systems, and cytokines.
• The reflex pathway steps are:
  • Stimulus
  • Sensor
  • Input Signal
  • Integrating Center
  • Output Signal
  • Target
  • Response.

Neural Reflexes

• Reflex are initiated by:
  • Central or peripheral receptors
  • Threshold stimulus.

Control systems

• The control system components varies in their complexity (simple to complex pathways).
• Reflex pathways are also of 3 types:
  • Neural
  • Endocrine
  • Neuroendocrine.

Reflex Speeds

• Physiological reflex control pathways are also varies on their speeds because they are are mediated by 3 means:
  • The nervous system
  • The endocrine system
  • A combination of the two.

Comparisons

• Each control system has some defining features that differ:
  • Specificity
  • Speed
  • Nature of signal
  • Action duration
  • Intensity coding.