Cellular Responses to Environmental Signals and Stresses Notes

Cellular Responses to Environmental Signals and Stresses

Cell Filaments and Movement

  • Cellular responses to environmental signals and stresses involve various mechanisms, including cell filaments and movement.

Mechano Receptors

  • Mechano receptors play a role in sensing mechanical stimuli.

Smell / G-Protein-Coupled Receptors (GPCRs)

  • Olfactory processes are mediated by G-protein-coupled receptors (GPCRs).

Transient Receptor Potential (TRP) Channels

  • Transient receptor potential (TRP) channels are involved in cellular responses.

Stresses - Cellular Response to Temperature / Heat

  • Cells respond to temperature changes and heat stress.

Cellular Response to Physical & Psychological Stresses

  • Cellular responses are triggered by physical and psychological stresses.

Short Intro to Epigenetics

  • Epigenetics are briefly introduced.

Cellular Response to Starvation (Autophagy)

  • Cells respond to starvation through autophagy.

Objectives

  • Explain 'chemotaxis.'

  • Know which receptors and organs detect pheromones.

  • Know what mechano receptors and heat shock proteins are.

  • Know what transient receptor potential (TRP) cation channels do.

  • Understand how stresses can alter gene expression and cell behavior.

  • Explain 'autophagy.'

Eukaryotic Cell

  • A eukaryotic cell consists of various components: actin filaments, peroxisome, microtubule, centrosome, ribosomes, Golgi apparatus, chromatin (DNA), nuclear pore, nucleolus, extracellular matrix, nuclear envelope, vesicles, lysosome, intermediate filaments, plasma membrane, nucleus, endoplasmic reticulum, and mitochondrion.

Cytoskeletal Filaments

  • Cytoskeletal filaments are crucial for cell structure and function.

Fibroblast Crawling

  • Fibroblasts crawl using different arrangements of actin filaments.

Protein Filaments: Change of the Cell Shape

  • Protein filaments such as cytoskeletal filaments change the cell shape.

Cytoskeletal Filaments are Dynamic and Adaptable

  • Cytoskeletal filaments are dynamic and undergo reorganization during cell division and cell migration.

Chemotaxis Model

  • Chemotaxis involves a directional response where cells balance cytoskeletal architecture and the external gradient of a chemical signal.

  • A chemotactic peptide (CP) binds to its GPCR, leading to a signaling cascade that accumulates PIP3 on the membrane.

Chemotaxis Definition

  • Chemotaxis is the directed movement of a cell towards or away from a diffusible chemical (chemoattractant).

Signals Released into the Environment - Pheromone

  • Pheromones are signals released into the environment.

Olfactory Receptors

  • Olfactory receptors are present in the olfactory bulb and nasal cavity.

  • Afferent nerve fibers (olfactory nerve) transmit signals to the olfactory tract.

  • The olfactory mucosa contains basal cells, olfactory receptor cells, and supporting cells, covered by a mucus layer and cilia.

Olfactory Pathways

  • Olfactory pathways include the olfactory bulb, olfactory tract, thalamus, and cortex.

  • These pathways are responsible for conscious perception and discrimination of smell.

  • The limbic system is involved in behavioral reactions associated with feeding, mating, and direction orienting.

Ligands and Functions for Mammalian Olfactory Organs and Receptors

MOE (Main Olfactory Epithelium)

  • Receptors: ORs (Olfactory Receptors)

  • Origin: Food, environment

  • Proposed Functions: Odor recognition, discrimination, attraction/repulsion

VNO (Vomeronasal Organ)

  • Receptors: V1Rs

  • Origin: Urine

  • Proposed Functions: Conspecific recognition, male sexual behavior, maternal aggression, regulation of female estrous cycles, stress level indicator

  • Receptors: V2Rs

  • Origin: Urine, bodily secretions

  • Proposed Functions: Mate recognition in the context of pregnancy

ENT (Other Olfactory Organs: Exocrine Gland-Secreting Peptides)

  • Receptors: PIR

  • Origin: Tears from specific genders or strains

  • Proposed Functions: Information about gender and individual identity, conspecific recognition

MOB (Main Olfactory Bulb)

  • Receptors: Sulfated steroids

  • Origin: Female urine

  • Proposed Functions: Indication of stress levels

GG (Grueneberg Ganglion)

  • Receptors: Formyl Peptide Receptors, CRAMP, lipoxin, uPAR peptides

  • Origin: Gram-negative bacteria, immune system peptides

  • Proposed Functions: Indication of pathogenicity or health status

SO (Septal Organ of Masera)

  • Receptors: TAARS, V2r83

  • Origin: Stressed conspecifics

  • Proposed Functions: Alarm pheromones, avoidance of dangerous situations

AON (Anterior Olfactory Nucleus)

  • Receptors: ORs

  • Origin: Food, environment

  • Proposed Functions: Alerting role or "mini-nose"

Vomeronasal Organ (VNO)

  • Mammalian pheromones are detected by the olfactory system, including the main olfactory epithelium (MOE) & the vomeronasal organ (VNO).

  • In 1959, Karlson & Luscher defined pheromone as a chemical released by one organism that modulates the behavior or physiology of another organism of the same species.

G-Protein-Coupled Receptors (GPCRs)

  • GPCRs are physiologically important membrane proteins that sense signaling molecules.

  • GPCRs have similar structures but are highly specific to their stimulus (light, smell, etc).

Mechanoreceptors

  • Mechanoreceptors include hair cells and Pacinian corpuscles, which respond to mechanical stimuli such as touch.

Mechanosensory Neurons in Mice

  • Mechanosensory neurons in mice expressing the G-protein-coupled receptor MRGPRB4 detect stroking of hairy skin.

Transient Receptor Potential (TRP) Cation Channels

  • TRP channels function as environmental sensors primarily through Ca2+Ca^{2+} signaling.

  • TRP channels act as thermosensors in sensory nerves and can be activated by agonists or natural stimulants.

Temperature-Dependent Sex Determination (TSD)

  • The thermosensitive transient receptor potential TRPV4 protein of Alligator mississippiensis may promote male development via temperature.

  • Incubation of American alligator eggs at 33∘C33^\circ C produces mostly males, while incubation at 30∘C30^\circ C produces mostly females.

Stress

  • Stress is a generalized, nonspecific response to any factor that overwhelms the body’s ability to maintain homeostasis; it is induced by a stressor.

  • A stressor is the factor or agent inducing stress.

Types of Stressors

  • Physical (trauma, heat, cold)

  • Chemical (reduced O2O_2 supply, acid-base imbalance, nutritional deficit/starvation)

  • Physiological (hemorrhagic shock, pain)

  • Psychological/emotional (anxiety / fear)

Stress: Temperature

Local Temperature Changes

  • Heat causes arteriolar vasodilation (widening of small diameter blood vessels).

  • Cold causes arteriolar vasoconstriction (narrowing of small diameter blood vessels).

Therapeutic Applications

  • Heating promotes blood flow, increasing oxygen and nutrients.

  • Cooling reduces blood flow, reducing inflammation (triggered by histamine).

Stress: Temperature / II

  • Heat can cause denaturation, a dramatic change in the conformation of nucleic acids or proteins, resulting in loss of biological function.

Stress: Temperature / IV

  • A molecular event during sudden temperature elevation is the induction of heat shock proteins (HSPs).

  • HSPs are highly conserved molecular chaperone proteins that facilitate correct protein folding or refolding.

  • Example: Zebrafish expression of HSPs 48 hours after fertilization.

Stress: Temperature / V - Structure and Function of Hsp60

  • A misfolded protein is captured by the Hsp60 protein complex.

  • Binding of ATP and a protein cap increases the diameter of the "barrel rim," allowing the protein to fold into its functional structure.

Stress: Heat Shock Proteins Summary

  • Heat shock proteins (HSPs) are up-regulated in response to sudden temperature elevation and other stressors, including:

    • Heavy metals

    • Ischemia (insufficient blood supply to an organ)

    • Alcohol

    • Ultraviolet light exposure

  • These proteins help to properly fold other proteins perturbed by such stressors.

Stress: Physical & Psychological / Emotional

  • Physical stressor: an external challenge to homeostasis.

  • Psychological/emotional stressor: the anticipation (justified or not) that a challenge to homeostasis looms.

  • Both types of stressors activate the fight-or-flight response and the HPA axis.

  • Glucocorticoids (adrenal steroid hormones) prepare the body for strenuous physical activity in an emergency.

Stress: Glucocorticoids and Gene Expression

  • Glucocorticoids bind to glucocorticoid receptors (GR) in the cytoplasm.

  • The GR translocates to the nucleus and affects gene transcription via transcription factors(TF).

  • A single gene regulatory protein (i.e., the glucocorticoid receptor) can regulate many genes coordinately.

Stress: Chronic Psychological / Emotional

  • Socially stressed animals consistently have elevated glucocorticoid levels and enlarged adrenal glands.

  • Neurobiological changes include inhibition of neurogenesis, dendritic atrophy, and impaired synaptic plasticity.

Early Life Environment

  • Early life environment impacts lasting epigenetically mediated changes in stress response.

  • In rats, variations in maternal behavior (licking/grooming and nursing arched-back vs. blanket posture) influence offspring stress responses.

  • Offspring of 'high-LG-ABN' mothers are less fearful and show more modest responses to acute stress due to altered expression of genes regulating stress responses.

Maternal Care and Glucocorticoid Receptor (GR) Gene

  • Maternal care permanently alters the activity of the Glucocorticoid Receptor (GR) gene in the hippocampus.

  • Epigenetic mechanisms establish lasting changes in gene expression following environmental experiences in early life.

Stress: Starvation

  • Undernourishment is prevalent in many regions globally.

  • Starvation triggers cellular survival mechanisms.

Stress: Starvation / II

  • Eukaryotic cells are equipped with mechanisms to survive when starved of nutrients.

  • Cells undergo intracellular protein degradation.

Intracellular Protein Degradation

  • Intracellular protein degradation enables the provision of amino acids under adverse conditions, rapid adaptation to environmental changes, intercellular communication, signal transduction, control of intracellular traffic, morphogenesis, control of proliferation and differentiation of cells, cell death, and aging.

Autophagy

  • Autophagy is a process in which cytoplasmic components are broken down to supply materials for the synthesis of essential molecules under nutrient-limiting conditions.

  • In times of nutrient starvation, eukaryotic cells increasingly digest their own proteins and cellular organs.

  • Autophagy means "self-eating."

Stress: Starvation: Increased Rate of Autophagy / I

  • Autophagy takes place in special organelles called autophagosomes.

  • The process starts with the engulfment of cellular components and organelles by a double membrane.

Stress: Starvation: Increased Rate of Autophagy / II

  • The autophagosome fuses with a lysosome and digests the content.

  • Lysis is an act of loosening or dissolution.

  • A lysosome is a membrane-bounded organelle containing digestive enzymes with an acidic pH.

Stress: Starvation: Increased Rate of Autophagy / III

  • Autophagosomes remove misfolded proteins, damaged organelles, or disease-causing bacteria.

  • Intracellular protein degradation differs from dietary protein digestion.

  • Digested proteins were synthesized by the organism.

  • Autophagy is one of several cellular mechanisms leading to intracellular protein degradation.