Biology Chapter on Homeostasis and Signaling

Cell Signaling

• Lecturer: Dr. Michelle Kuzma
• Adapted from: Dr. Danuta Mielżyńska-Švach
• Course: Molecular Biology
• Academic Year: 2024/2025

Homeostasis

• Organisms maintain a stable internal environment to cope with external variability.
• Homeostasis is the process of maintaining internal stability (homeo - similar, stasis - state).
• When homeostasis is disrupted, the organism compensates.
• Successful compensation restores homeostasis.
• Unsuccessful compensation disrupts homeostasis and can lead to disease.

Homeostasis Components

• Extracellular fluid (ECF): Links the external environment to cells; serves as a connection.
• Intracellular fluid (ICF): Located within cells; includes fluid inside cells and between cells (intercellular or interstitial) and fluid within blood vessels (intravascular).

Homeostasis Imbalance

• Homeostasis is not equilibrium, but a dynamic steady state.
• The composition of ECF and ICF differ; showing an established imbalance, not equilibrium.
• Specific ion concentrations (e.g., Na+, Cl-, K+) differ between ECF and ICF.

Role of Homeostasis in Multicellular Organisms

• Cells within tissues, tissues within organs, and systems within an organism must coordinate their activities to maintain homeostasis.
• Cellular cooperation is needed for this.
• Cells communicate via intercellular communication (e.g., cell signaling).

Intercellular Communication

• Essential for cell survival, division, differentiation, and death.
• Two basic types of signals:
  • Electrical: Related to membrane potential changes.
  • Chemical: Chemical compounds (molecules) secreted into the extracellular space.

Cell Communication Methods

• Local Communication:
  • Juxtacrine: Direct contact between cells (e.g., gap junctions).
  • Paracrine: Signaling molecules diffuse to nearby cells.
  • Autocrine: Signal molecules act on the same cell that secreted them.
• Distant Communication:
  • Endocrine: Hormones are secreted into the blood stream for distant target cells.
  • Neuronal: Electrical signals are converted to chemical signals (neurotransmitters) at synapses.

Types of Cell Communication

• Juxtacrine: Direct transfer of molecules via gap junctions. Cells target cells connected by gap junctions. Gap junctions act as intercellular channels.
• Paracrine: Signaling cell targets a nearby cell with release of molecules into extracellular fluid to act on neighboring cells.
• Autocrine: Molecules released by cells into the intercellular fluid, affecting the same cell that secreted them. A cell targeting itself..

Types of Cell Communication

• Endocrine: Hormones are secreted into the bloodstream, distributed across the body via the circulatory system, affecting distant target cells.
• Neuronal (synaptic): Combination of electrical and chemical signals used for long-distance communication.

Neurotransmitters and Neurohormones

• Neurocrine molecules, secreted by neurons, are divided into:
  • Neurotransmitters: Signal across synaptic clefts with rapid effect (fast effect)
  • Neurohormones: Diffuse into the bloodstream for slower, widespread effects (slower effect).

Cellular Receptors

• Specialized proteins that receive, transform, and transmit information from the external environment to effectors within a cell.

Signal Molecules

• Classified as those that pass through the cell membrane or do not.
• Lipophilic (hydrophobic): Intracellular receptors (e.g., steroid hormones, Thyroid hormones, vitamin D, retinoic acid).
• Hydrophilic (water soluble): Cell membrane receptors.

Intracellular Receptors

• Located in the cytoplasm or nucleus.
• Ligands are small, hydrophobic molecules that diffuse across the cell membrane.
• Active ligand-bound receptor only in the nucleus.
• Regulate gene expression (transcription).
• Composed of several elements such as ligand binding domain, DNA binding domain etc.
• Bind to the hormone response element sequence in target genes.
• Often dimeric (homo- or hetero-dimers)
• Include receptors for lipophilic hormones (e.g., steroid hormones, thyroid hormones, vitamin D, and retinoic acid) as well as for ligands yet to be identified ("orphan" receptors).

Cell Surface Receptors

• Proteins located on or within the target cell membrane.
• Ligands are large, hydrophilic/charged molecules that cannot diffuse through the cell membrane.
• Transduce extracellular signals into intracellular signals, altering cell behavior.
• Types include:
  • Ion channel-linked receptors: Change membrane potential, affecting ion permeability. (Fast response)
  • G protein-coupled receptors (GPCRs): Initiate a cascade of events involving secondary messengers. (Slower response).
  • Enzyme-linked receptors: Have intrinsic enzymatic activity or associate with enzymes.

Ion Channel-Linked Receptors

• Binding of a ligand causes a change in channel conformation, altering membrane potential (permeability) and ion flow.
• Respond quickly.
• Examples: For neurotransmitters.

G Protein-Coupled Receptors (GPCRs)

• Large family of receptors.
• Involved in signal transduction via secondary messengers.
• Have seven transmembrane helices (7TM receptors).
• Combine with ligands to activate secondary messengers.
• Examples: adenylyl cyclase and phospholipase C.

G Proteins

• Located on the cytoplasmic side of the cell membrane.
• Composed of three protein subunits (α, β, γ).
• GDP-bound in the inactive state; GTP-bound in the active state.

Protein Kinase

• Enzymes that phosphorylate proteins causing conformational changes, alter protein activity and binding ability.
• ~30% of proteins are regulated through this way.
• Often involved in metabolic signal pathways.

Secondary Messenger Molecules

• Molecules produced to relay signals initiated from G proteins into the cell.
• Examples: cAMP, IP3, DAG.

Adenylyl Cyclase

• Enzyme that produces cAMP, a secondary messenger in G protein signaling pathways.
• Activated by specific ligands.
• cAMP signaling pathway leads to protein kinase A (PKA) activation; resulting in downstream effects including glycogen breakdown, gene expression alteration etc..

Phospholipase C (PLC)

• Enzyme that produces IP3 and DAG, secondary messengers in G protein signaling pathways.
• Activated by specific ligands.
• Downstream effects include altered intracellular Ca2+ concentration, activation of protein kinase C (PKC), and downstream phosphorylation cascades.

Enzyme-Linked Receptors

• Receptors that have catalytic activity as their own or are associated with enzymes.
• Typically involved in slower responses that involve gene expression changes.
• Includes tyrosine kinase and serine/threonine kinase receptors.

Tyrosine Kinases

• Receptor family activated by growth factors (e.g., FGF, EGF, PDGF, VEGF).
• Tyrosine residues are phosphorylated upon ligand binding and activation of kinase activity; forming dimers.
• Triggers downstream signaling cascades such as Ras activation.

Ras Protein

• Monomeric G protein.
• Usually bound to the cell membrane.
• Involved in numerous signalling pathways.
• Switches between inactive (bound to GDP) and active (bound to GTP).
• Activation often initiated by tyrosine kinase pathways.
• It is involved in the downstream phosphorylation cascade.

Phosphorylation Cascade

• A series of protein phosphorylations.
• Often initiated by Ras and carry the signal further.
• Usually involves serine/threonine kinases like MAP kinases.

PI3K/Akt Pathway

• Growth and survival pathway activated by growth factors.
• Involves PI3 kinase, PKB/Akt, and other proteins.
• Regulates cell growth, survival, and proliferation.

Signal Integration

• Ability of cells to combine signals from multiple sources to regulate responses.

Cell Signal Response

• Cell signal response can be fast or slow depending on the processes involved.
• Rapid response (e.g., motility changes, metabolism) requires altering protein function.
• Slower responses (e.g., growth, differentiation) require protein synthesis or gene expression changes.

Test your understanding of homeostasis and the mechanisms that maintain it in multicellular organisms. This quiz covers the roles of intercellular communication, signaling molecules, and the physiological responses involved in homeostasis. Challenge yourself with questions that explore the interactions between cells and their environment.