Cell signaling is crucial for unicellular and multicellular organism survival.
In unicellular organisms, cell signaling dictates responses to environmental changes.
In multicellular organisms, it coordinates individual cell activities to support overall functional integrity.
The similarity in signaling pathways and molecules across all organisms suggests an evolutionary origin in prokaryotes that was later adopted by eukaryotes, providing evidence for evolution.
Signaling occurs through signal transduction pathways, which convert external signals into cellular responses.
Cell signaling consists of three main stages:
Reception: Detection of signaling molecules (ligands).
Transduction: Transformation of the signal into a cellular response.
Response: The change in cellular behavior or function.
Ligands: Molecules that bind to receptor proteins on target cells, initiating a response.
Target Cells: Cells equipped with specific receptor proteins that respond to the ligands only.
Receptor Specificity: Only target cells with the necessary receptors can respond to a specific signal.
Signaling begins when a ligand binds to its receptor protein, typically non-covalently and reversibly.
Ligand-binding domains of receptors interact specifically with chemical messengers, which can include peptides, small chemicals, or proteins.
The binding is reversible, allowing cells to halt the response once it is no longer needed.
Intracellular Receptors: Located within the cytoplasm or nucleus, binding ligands that are small or nonpolar (e.g., steroid hormones).
Membrane Receptors: Located on the cell surface with large or polar ligands that cannot diffuse through the membrane:
G-Protein Linked Receptors
Ligand-Gated Ion Channels
Activated by small or hydrophobic ligands that cross the membrane (e.g., testosterone, estrogen).
These receptors can function as transcription factors, regulating gene expression by activating specific genes inside the cell.
These receptors are closed channel proteins that open upon ligand binding, allowing ions to flow across the membrane, altering ion concentrations.
Example: Acetylcholine receptors on skeletal muscle cells facilitate Na+ and Ca2+ ion influx, triggering muscle contraction.
These receptors rely on G-proteins that mediate cellular signaling following ligand binding.
G-proteins are activated upon GDP-to-GTP exchange, leading to downstream signaling events triggering specific cellular responses.
Key trait: All G-protein linked receptors feature 7 transmembrane domains, highlighting an evolutionary commonality.
Ligand binding initiates a signal transduction pathway, amplifying the signal through multiple steps.
Multistep pathways efficiently regulate cellular responses, often involving phosphorylation cascades and secondary messengers.
Phosphorylation mechanisms regulate protein activity by adding phosphate groups, making proteins active.
A phosphorylation cascade involves a series of sequential protein activations, enhancing signal transduction efficacy.
These are small, hydrophilic molecules that relay signals from receptors to target molecules within the cell:
Examples include cyclic AMP (cAMP) and calcium ions (Ca2+).
cAMP activates protein kinase A, leading to phosphorylation cascades for amplified responses.
Signal transduction pathways exhibit amplification, where a single ligand can lead to the activation of extensive signaling cascade outputs (e.g., 1 epinephrine molecule may release 100 million glucose molecules).
Cellular response specificity is determined by the ensemble of receptors and relay proteins present, leading to different responses in different cell types to identical signals.
Examples:
Liver cells break down glycogen when exposed to epinephrine while heart muscle cells increase contraction.
Cells respond to environmental signals in a multitude of ways:
Opening of ion channels altering ion concentration and electrical potential.
Changes in gene expression through transcription factor activation.
Regulation of enzyme activity impacting cellular metabolism.
They enable responses to signals that cannot cross the plasma membrane.
Diversity in pathways allows tailored cellular responses.
Amplification of signals ensures efficient responses, enhancing evolutionary fitness.
Disruptive conditions in signal transduction can lead to harmful effects; for example, anthrax toxins increase cAMP levels, impairing proper cell signaling responses.
Insulin signaling pathways can become defective, leading to impaired glucose uptake as observed in Type 1 and Type 2 diabetes.
Cells communicate through direct contact (juxtacrine) or through signaling molecules over short (autocrine and paracrine) and long distances (endocrine).
Juxtacrine signaling requires direct cell contact; examples include cell junctions (plasmodesmata and gap junctions).
Cell surface markers can serve as ligands initiating signaling between adjacent cells.
Local regulators target nearby cells; include autocrine signaling (self-targeting) and paracrine signaling (neighboring cell targeting).
Specialized examples: Morphogens provide positional information during embryonic development, influencing cell differentiation based on concentration gradients.
Quorum sensing in bacteria allows communication based on population density, affecting gene expression in unison.
Endocrine signaling utilizes hormones secreted into the bloodstream to relay signals across the body; many hormones are protein-based, with exceptions like steroid hormones.
Insulin and human growth hormones exemplify key long-distance signaling molecules vital for metabolic regulation and growth, respectively.
Homeostasis is the capability of organisms to maintain stable internal conditions amidst external shifts.
Defined as dynamic homeostasis due to constant regulatory interactions.
Negative feedback maintains homeostasis by counterbalancing changes to a set point through a stimulus-response mechanism.
Example: Thermoregulation involves blood vessel dilation/constriction and sweat/or shivering responses.
In contrast, positive feedback mechanisms amplify processes essential for completing specific biological functions, moving away from homeostasis temporarily.
Examples include childbirth, where oxytocin release promotes uterine contractions, and fruit ripening, where ethylene accelerates surrounding fruit ripening.