2.5 Cellular communication 1

Cells and Tissues

Cellular Communication

• Fundamental aspect of organismal complexity and functionality.

Importance of Communication

• Critical for maintaining homeostasis and coordinating body systems:

  • Nervous System: Fast-acting communication via electrical signals.

  • Immune System: Regulates response to injury and infection.

  • Digestive System: Coordinates digestion and nutrient uptake.

  • Cardiovascular System: Distributes hormones and nutrients.

  • Musculoskeletal System: Controls movement and response to stimuli.

  • Integumentary System: Protects and senses environmental changes.

  • Excretory System: Regulates waste elimination.

  • Reproductive System: Controls reproduction and development.

  • Endocrine System: Hormonal communication for long-lasting effects.

  • Respiratory System: Manages gas exchange efficiently.

How Cells Talk

Signal Perception

1. Ligand Signal: External signaling molecules (ligands) bind to receptors on target cells.

   • Molecule- Receptor Interaction: Initial communication occurs when ligands bind to specific receptors.

Intracellular Signal Transduction

2. Signal Transduction: Converts extracellular signals into intracellular responses.

   • Relay Molecules: Amplifies the signal through a cascade of intracellular signaling events.

Cellular Response

3. Cellular Response: Ultimately, cellular actions are taken based on the initial signals, including changes in gene expression, growth, metabolism, and other cell functions.

Types of Cell Signaling

Autocrine Signaling

• Cells respond to signals that they themselves release.

Contact-Dependent Signaling

• Requires direct contact between signal-secreting and target cells.

Paracrine Signaling

• Signals diffuse across a short distance to nearby cells.

Endocrine Signaling

• Signals are distributed throughout the body via the bloodstream.

Ligands and Receptors

Ligands

• Extracellular Chemical Signals: Such as proteins, lipids, and ions secreted by signaling cells.

  • Types of Ligands: Can be hydrophobic (lipid-soluble) or water-soluble.

• Secreted by the siganalling (sensory) cell

• local and long distance messengers

• bind to the target cell

  • Reactions (receptor-ligand binding) can be:

    • Reversible (varying time frame)

    • Irreversible

• Receptor agonist

  • Ligand binds - activates → cellular response

• Receptor antagonist

  • Ligand bind - no effect → prevents agonist binding

• Hydrophobic ligand

  • Lipid soluble, cross the plasma membrane

  • Steroid hormaones, derived from cholesterol

    • Sex steroids

      • Osetrogens

        • A group of sex steroids that are primarily involved in the female reproductive system and have various physiological effects, including regulation of the menstrual cycle, maintenance of pregnancy, and development of secondary sexual characteristics. They are lipid-soluble and derived from cholesterol.

      • Androgens

        • A group of sex steroids that primarily influence male characteristics and reproductive activity. They are responsible for the development of male physical traits such as facial hair, deep voice, and muscle growth. Testosterone is the most well-known androgen, regulating various functions in both males and females.

      • Progesterone

        • A steroid hormone involved in regulating various functions in the female reproductive system, including preparation of the uterine lining for pregnancy, maintenance of pregnancy, and regulation of the menstrual cycle. It plays a critical role in promoting gestation and supporting early stages of fetal development.

    • Corticosteroids

      • Glucocorticoids (cortisol)

        • A class of corticosteroids that play a vital role in the body's response to stress by regulating metabolism and inflammation. Cortisol is the most well-known glucocorticoid, influencing a variety of functions including glucose metabolism, immune response modulation, and blood pressure regulation.

      • Mineralocorticoids (aldosterone)

        • A class of corticosteroids involved in the regulation of electrolyte and water balance, primarily acting on the kidneys to enhance sodium reabsorption and potassium excretion. The most well-known mineralocorticoid is aldosterone, which plays a key role in regulating blood pressure and maintaining fluid balance.

    • Eicosanoid hormones

      • A group of bioactive lipids derived from arachidonic acid, which is a polyunsaturated fatty acid. Eicosanoids include prostaglandins, thromboxanes, and leukotrienes, which play crucial roles in various physiological processes such as inflammation, immune responses, and the regulation of blood flow.

      • Prostaglandins

        • A group of lipid compounds that are derived from fatty acids and have diverse physiological effects. They are involved in various body functions, including the regulation of inflammation, blood flow, and the formation of blood clots. Prostaglandins can also play a role in the process of labor and delivery in pregnancy, as well as in the regulation of the menstrual cycle.

    • Throid hormones

    • Calcitriol - active form of Vitamin D

    • Vitamin A

    • Nitric oxide (gas) - alters intracellular target enzyme activity

• Water soluble ligands

  • Binds to extracellular receptors

    • Peptides and small proteins

      • Cytokines, growth factors

      • Extracellular matrix (ECM) components

        • Fibrous ECM proteins, glycoroteins, proteoglycans, polysaccharides

  • Water-soluble hormones

    • Amine hormones

      • Catecholamines

        • A group of amine hormones that includes epinephrine (adrenaline), norepinephrine (noradrenaline), and dopamine. These hormones play significant roles in the body's response to stress and are involved in regulating heart rate, blood pressure, and glucose metabolism. They are produced in the adrenal glands and are crucial for the fight-or-flight response.

      • Histamine

        • A biologically active amine involved in various physiological functions. It plays a key role in immune responses, regulation of gastric acid secretion, and neurotransmission. Histamine is released during allergic reactions and can cause symptoms such as itching, swelling, and redness by increasing blood vessel permeability.

      • Serotonin

        • A neurotransmitter that is involved in various functions in the body, including regulation of mood, appetite, and sleep. It is derived from the amino acid tryptophan and is known for its role in feelings of well-being and happiness, as well as influencing gastrointestinal function and cardiovascular health.

      • Melatonin

        • A hormone that regulates sleep-wake cycles and circadian rhythms. It is primarily produced in the pineal gland in response to darkness, promoting sleep by signaling to the body that it is time to rest. Melatonin levels typically rise in the evening and fall in the morning, playing a crucial role in the body's internal clock.

    • Peptide hormones

      • Antidiuretic hormone

        • A hormone produced by the hypothalamus and released by the posterior pituitary gland, which plays a crucial role in regulating water balance in the body by promoting water reabsorption in the kidneys. ADH helps to concentrate urine and maintain blood pressure by reducing urine output.

      • Oxytocin

        • A hormone produced by the hypothalamus and released by the posterior pituitary gland that plays key roles in social bonding, reproduction, childbirth, and the initiation of lactation. It is often referred to as the "bonding hormone" due to its role in promoting attachment and emotional bonding between individuals, particularly between mothers and their infants.

      • Secretin

        • A hormone produced by the S cells of the duodenum in the small intestine, which plays a crucial role in regulating the body's pH. It stimulates the pancreas to release bicarbonate, neutralizing the acidity of chyme entering the small intestine from the stomach, thereby facilitating proper digestion and enzymatic activity.

    • Protein hormones

      • Insulin

        • A hormone produced by the pancreas that plays a crucial role in regulating glucose metabolism. It facilitates the uptake of glucose by cells for energy production, promotes the storage of glucose as glycogen in the liver and muscles, and influences fat and protein metabolism. Insulin is essential for maintaining normal blood sugar levels and is particularly important for individuals with diabetes, who may have insufficient insulin production or action.

      • Human Growth hormone

        • A peptide hormone produced by the pituitary gland that is essential for growth, cell repair, and metabolism. HGH stimulates growth in children and adolescents and helps maintain tissues and organs throughout life. It plays a critical role in protein synthesis, fat metabolism, and glucose regulation. HGH is also important for muscle and bone development.

• Other molecules

  • Natural or synthetic

    • Neurotransmitters

    • Gases (NO, CO)

    • Ions (CA2+, Na+, K+) - Essential for signal transduction and cellular communication.

    • Drugs

      • Target regulatory proteins

        • Enzymes, carrier proteins, ion channels and receptors

Receptors

• Specific Proteins:

  • Reside on or in target cells to initiate a response.

• Span the plasma membrane

• bind ligands

  • Released by the signalling cells

• Lock and Key Model: Highly specific interaction between ligands and receptors.

  • Recetor — ligand interactions are highly specific

  • A single ligand

    • Can bind to multiple receptors

    • Elicits different responses for different cell types

  • Types of Receptors:

    • Ligand-Gated Ion Channels: Open in response to binding; allowing ion influx.

    

    • Enzyme-Linked Receptors: Activate enzymes upon ligand-binding; lead to internal signaling changes.

    

    • G Protein-Coupled Receptors: Active internal signaling pathways upon activation; largest group of receptors.

    

    • Intracellular Receptors: Bind lipid-soluble ligands; influence transcription and translation processes.

Intracellular receptors (DNA -Linked nuclear receptors

• Internal receptors

  • Consist of a binding domain and a DNA-binding domain (zinc finger)

• Bind lipid soluble ligands

  • Ligand diffuses across the plasma membrane

  • binds a recptor in the cytoplasm or the nucleus

• The ligand-receptor complex

  • binds DNA

  • alters transcription and translation

  • Slow acting - response hours - days

Receptor ion channels (Ionotropic receptors)

• Cell surface receptor

• On binding of ligands

  • Changes shape

  • Channel opens

  • Ions flow into the cell

  • Alter intracellular compositions and activity of the cell

  • Fast acting

  • Channel made up of combination of subunits

    • α, β, γ and δ

Enzyme linked receptors (Kinase-linked receptors

• Cell surface receptor

  • Receptor is coupled to a (signal transmitting) enzyme

• On binding of ligands (Cytokines,growth factors, hormaones)

  • Change in shape

  • Enzyme activation

  • Chemical reaction initiated

G-protein coupled receptors (Metabotropic receptors)

• cell surface receptor

• Response (100ms to seconds)

• Largest and most diverse group of receptors

• Enzyme linked

• G-protein

  • Diffusible through membrane but bound to intracellular surface

  • Consists of 3 subunits (α, β and γ)

  • Inactive state

    • Form heterotrimeration upon ligand binding, leading to a conformational change that activates the receptor and initiates downstream signaling pathways.

    • This activation often results in the exchange of GDP for GTP on the α subunit, which then dissociates from the β and γ subunits to interact with various effector proteins.

  • Active state

    • Subunits dissociate , allowing the α subunit to modulate the activity of downstream signaling molecules, thereby propagating the signal within the cell.

    • (α subunit and β-γ

      subunit)

    • α subunit bound to GTP

G-protein coupled receptors (Intracellular signaling cascade)

• G-protein → types

  • α subunit dependent

  • Different characteristics

  • influence different

    • Effector systems

      • Adenylate cyclase

      • phospholipase C (PLC)

    • Second messenger systems

      • Cyclic adenosine monophosphate (cAMP)

      • Protein Kinase A (PKA)

      • Diacylglycerol (DAG)

      • Inositol triphophate (IP3)

  • β-γ subunit - dimer

  • Influence other signalling pathways

    • Phospholipases

    • Ion channels

    • Lipid kinases

G-protein coupled receptors (Metabotropic receptors)

• Cell surface receptor

• Response (100ms to seconds)

• Largest and most diverse group of receptors

• Enzyme linked

• G-protein

  • Diffusible through membrance but bound to intracellular surface

  • Consist of 3 subunits (α, β and γ)

  • Activation of enzymes

  • Cascade of events involving activation of secondary proteins

  • amplification of signal

Mechanisms of Cellular Response

• Fast-Acting Responses: Ion channels open rapidly upon ligand binding; alterations in intracellular ion concentrations.

• Slow-Acting Responses: Intracellular receptors influence transcription and changes may take hours to days.

Second Messenger Systems

• Receptor-ligand complex activates an amplifier enzyme

  • Results in activation of a single signal molecule

• Amplifier enzymes (effector system)

  • Adenylyl Cyclase: Produces cAMP as a secondary messenger.

  • Phospholipase C: Produces IP3 and diacylglycerol, leading to intracellular calcium release.

• Second messenger molecules

  • cAMP, IP3, Ca2+, and diacylglycerol play crucial roles in mediating cellular responses to various extracellular signals.

• Cellular responses

  • Altering the activity of enzymes

  • ion Channels

  • transporters

  • genes

Factors Influencing Cellular Response

• Type of ligand, receptor, and intracellular signaling pathways dictate variability in cellular responses:

  • Responses Can Include: Cell growth, differentiation, movement, or apoptosis.

Integrated Communication in Body Systems

• Various body systems communicate through hormonal pathways and neural networks to maintain homeostasis, especially during stress (e.g., exercise):

  • Central Command and Regulation: Integrated circuitry manages complex physiological transitions pertaining to metabolism and circulation, facilitating coordinated responses across multiple systems.