Cellular Signal Reception & Transduction

• Cells identify signals via distinctive receptors
• Animal cells respond via internal interactions to signals

Syllabus Content Overview

• HL content includes receptors, quorum sensing, hormones, localized/distant signalling, receptors (transmembrane, intracellular), signal transduction, neurotransmitter receptors, G proteins, epinephrine receptors, receptors with tyrosine kinase activity, intracellular receptors affecting gene expression, effects of oestradiol/progesterone, and feedback regulation

Receptors

• Multicellular organisms (and bacteria) have to respond to stimuli and communicate
• They coordinate via chemical signalling molecules called ligands
• Ligands include proteins, peptides, amino acids, nucleotides, steroids, amines, and dissolved gases like nitrogen monoxide (NO)
• Chemical signalling ensures activities occur in the right cells and time
• Chemical signaling often affects gene transcription but not necessarily affecting all genes simultaneously
• Most ligands can't cross cell membranes, needing receptor proteins
• Receptor proteins are ligand-specific
• Ligands activate target cells, regulating cellular response and control
• The binding process transmits signals and generates intracellular proteins/messengers
• This can activates enzymes, often through phosphorylation

Signal Transduction

• A signal transduction pathway has critical functions
• Relay a signal onward for cell spread
• Amplify signals so that small ligand amounts produce large responses
• Detect and integrate signals from multiple pathways
• Distribute signals to multiple effector proteins for complex responses
• Primary transduction converts extracellular to intracellular messages
• Scaffold proteins improve reaction speed by holding proteins together
• The same signal molecule can trigger varied cellular responses in different cells
• Different cell types activate different genes, resulting in unique protein collections

Quorum Sensing

• Bacteria communicate by emitting, detecting, and responding to ligands
• In quorum sensing, bacteria activate genes as population density increases
• It relies on bacteria releasing signal molecules
• These molecules allow bacteria to communicate and coordinate behaviors at sufficient population sizes
• Autoinducers are quorum sensing signaling molecules detected inside cells or in cell membranes receptor
• When autoinducers bind to receptors, it activates or represses target genes
• Gene transcription include those for autoinducer synthesis

Animal Signalling Molecules

• Animal signaling molecules consist of hormones, neurotransmitters, cytokines and calcium ions.

Hormones

• Secreted by endocrine glands
• Carried through the circulatory system to target cells
• Hormones work to control cell metabolism e.g. sexual reproduction

Neurotransmitters

• Transmit signals between neurons or to target cells like muscle cells
• Released after action potential arrival
• Cytokines are small proteins that control the growth and differentiation of specific cells
• Some cytokines like a-interferon are produced by cells against viruses

Calcium Ions

• Ligands are mostly organic
• Some metal ions are involved in cells signalling, especially calcium
• Many ligands in animals cause signal transduction to increase cytoplasmic Calcium
• High concentration causes responses like muscle contraction, secretion, and cell division
• Calcium is a second messenger because cytoplasmic concentration is lower than outside

Chemical Diversity

• Extracellular molecules and ions act as ligands including metal ions, low molar mass compounds, steroids, peptides, and proteins

Hormone Classes

• Hormones act as ligands
• The three main classes are proteins, amines, and steroids
• Hormones can diffuse through the cell membrane to reach receptors in nucleus/cytoplasm such as progesterone and testosterone

Neurotransmitters

• Are a diverse group of chemicals, including amines, amino acids, polypeptides, and acetylcholine
• Neurons produce and release various neurotransmitters which allows cells to exert several influences at once
• Nitric oxide (NO) can act as a neurotransmitter or influence neurotransmitters

Signalling Effects

• Cells communicate via ligands for adjacent (local) / non-adjacent (long-distance) cells
• Local signalling involves direct contact between cells like in synapses where neurotransmitters transmit signals over short distances

Long-Distance Chemical Signaling

• Travel through the transport system to distant target cells
• Animal hormones in blood / plant hormones in sap travel through the body to interact with distant source receptors
• Hormones trigger a reaction cascade, changing cell metabolism
• Animal cells release hormone molecules into blood vessels to target cells which is known as endocrine signalling.
• Plant hormones travel through vascular tissue or by diffusion through the air as a gas.

Transmembrane vs Intracellular Receptors

• Receptor location depends on ligand properties
• Non-polar ligands diffuse through the phospholipid bilayer and access intracellular receptors
• Polar ligands can’t pass through the phospholipid bilayer and bind with surface receptors

Transmembrane Receptors

• Cell-surface receptors respond to charged, polar ligands
• Intracellular receptors are for lipid-soluble ligands like steroid hormones

Cell Surface Receptors

• Three regions: a ligand-binding region, a hydrophobic region extending through the membrane, and an intracellular region that transmits signals
• They have hydrophobic amino acids which allow them to embed in membranes
• Signals are relayed across the membrane which causes cell transduction

Intracellular Receptors

• Many lipid-soluble ligands diffuse throughout plasma membrane, diffuse into the nucleus, bind to DNA and initiate protein synthesis for reactions
• Steroid receptors are proteins in th cytoplasm
• Steroid hormones diffuse through the plasma membrane in cells
• If the cell is a target, hormone-receptor binds and moves to nucleus, acting as transcription factors to binding DNA, transcribed to translated proteins

Signal Transduction Pathways

• Signal transduction requires a series of changes in molecules, called relay molecules
• Signal transduction occurs by protein phosphorylation in a phosphorylation signal cascade and the release of secondary messenger
• The activated receptor activates the relay which activates another, until the protein produces the final response
• Molecules are protein kinases, acting on other kinases causing a Phosphorylation Cascade
• Relay molecules activate when phosphorylated/deactivated when dephosphorylated
• Phosphorylation/dephosphorylation acts as a molecular switch which activates certain activities on/off

Cellular Response

• Transduction pathway leads to regulating activity in the nucleus or cytoplasm of the cell.
• Depending on cell/ligand, cellular responses include protein activity, protein synthesis, enzyme activity, cytoskeleton rearrangements, and/or apoptosis cell death

Termination

• After cellular response, the signal is terminated

Sodium Ion Channels

• Composed of transmembrane protein subunits with aqueous pore across the lipid bilayer, lined by transmembrane regions
• Released Acetylcholine binds to receptor which causes the channel shape to change, causing Gate opens
• Allows sodium to flow across a concentration gradient
• This depolarises plasma membrane and changes membrane potential

G Proteins

• Activated by hormone or other ligand by its receptor
• Regulate bodily functions using intracellular signalling cascades
• Closely associated with G-protein receptor (GPCR) that binds to guanosine triphosphate/diphosphate
• GPCR's have a common structure of seven hydrophobic that span transmembrane
• Transduction is controlled by binding G proteins in the cytoplasmic loop of the receptors
• When inactive, it binds to GDP.
• When active, the receptor changes conformation activates G protein and exchanges for bound GTP.
• Once hormone is absent, GTP is hydrolyzed Back and inactive This causes cellular response

Epinephrine

• Released by adrenal glands and circulate in bloodstream, which prepares the body for activity
• Increases heart, enable increased oxygen and glucose to be delivered to Muscle Cells
• Vasoconstrictor, reduces blood supply and remains at site longer
• Epinephrine uses peptide receptors, which activates a chain reaction mediated by a second messenger in the cell called AMP (adenosine monophosphate and calcium ions)
• Second messengers amplify the strength in the signal.

Glucose

• Enzyme embedded in the cell surface enables ATP conversion to an increase of CAMP rapidly
• As CAMP increases, it amplifies signals
• Phosphodiesterase converts CAMP to AMP, thus terminating signals
• Hormone activates G protein which activates Adenylyl Cyclase which boosts production of CAMP - increase in CAMP activates PKA
• Glycogen activates, breaking down glycogen
• In Skeltal muscle, breakdown is caused by activating PKA which activated breakdown and causes Catalysts.

Relay

• Are activated kinases and proteins which catalyzes reactions

Kinase/Phosphorylase

• Relay proteins activated are Enzymes catalyze ATP to acceptors
• Relay proteins activated are Enzymes break down Glucose

Tyrosine Kinases

• Receptors are capable of enzymatic activity and activates signal ways

RTK’s

• May activate over ten different signal ways, help coordinate simultaneous activities
• An RTK is a polylipids chain with single protein that causes dimers to assemble a certain way - This causes the tails to bind and activates RTK by adding a phosphorus group through autophosphorylation.
• The tails leads to activation of specific proteins that can cause cells to respond

Insulin

• Informs cells of high glucose and to absorb it in liver
• Respond to signal by uptake, synthesis which decreases gluconeogensis
• RTK Signal allows body to uptake cells
• Embedded protein transports proteins to cell surface, it fuses and adds proteins that increase uptake in muscle cells
• Glycogen synthesis is catalyzed and bound to one molecule can synthesis of many units of glycogen

Intracellular Receptors

• Receptor molecules for testoterone signal receptors and travels nucleus to regulate expressions of genes (creates male characteristics)

Oestradiol

• Secreted into blood and travels the body, but depends on cell interaction
• Interacts in hormones due to brain interactions and releases homrones with are involved
• Once you release molecules it’ll create an reaction causing puberty and traits
• Is released and once the follicle becomes the corpus leteum produces inner tissue and endometrium

Feedback

• Pathway is controlled by feedback regulation
• Creates deviations
• In deviations of equilibrium causes the loop to return to initial conditions