C2.1 Chemical Signaling

C2.1.1 Receptors as proteins with binding sites for specific signaling chemicals

• Receptors have binding sites for signaling chemicals

  • Highly specific shape/chemical properties for ligands

  • Binding causes changes in the receptor → response to signal by target cell

C2.1.2 Cell signaling by bacteria in quorum sensing

• Quorum sensing:

  • Signaling molecules secreted at a low rate by all cells in population → reaches a threshold concentration

  • Sufficient binding of signaling molecules to receptors in a cell → changes gene expression

• e.g Bioluminescence in Vibrio fischeri

  • cells secrete a signaling molecule/autoinducer

  • When threshold is reached: production of enzyme that catalyzes a reaction that releases energy → light

C2.1.3 Hormones, neurotransmitters, cytokines and calcium ions as examples of functional categories of signaling chemical in animals

• Signaling systems have evolved repeatedly, leading to a wide range of chemical substances being used as signaling chemicals

• Ligand: small molecules that transmit molecules between/within cells

• Hormones

  • Signaling chemicals transported by bloodstream

  • Secreted by endocrine glands into blood capillaries

  • Widespread effects/target cells can be far apart

  • e.g. Insulin, thyroxin, testosterone

• Neurotransmitters

  • Chemicals that transmit signals across synapses

  • Synapse: junction between two neurons in the nervous system

  • Excitatory neurotransmitters stimulate nerve impulses

  • Inhibitory neurotransmitters inhibit nerve impulses

  • Signal conveyed quickly, short-lived effects

  • e.g. acetylcholine, norepinephrine, and dopamine

• Cytokines

  • Small proteins that act as signaling chemicals

  • Secreted by wide range of cells

  • Usually act on the cell that produced them or nearby cell

  • Cannot enter cells → bind to receptors in the plasma membrane

• Calcium ions

  • Used in cell signaling in both muscle fibers and neurons

  • Receives nervous impulse → calcium channels open in the membrane → diffuse out

  • Bind to proteins that block muscle contraction → allows muscle contraction to occur

C2.1.4 Chemical diversity of hormones and neurotransmitters

• All signaling chemicals must:

  • have a distinct shape and chemical properties so the receptor can distinguish between it and other chemicals

  • be small and soluble enough to be transported

• Chemical categories for hormones:

  • amines

  • peptides

  • steroids

• Chemical categories for neurotransmitters

  • amines

  • gases

  • amino acids

  • esters

C2.1.5 Localized and distant effects of signaling molecules

• Neurotransmitters are transported short distances (~20 nanometers)

• Hormones are transported in blood to all parts of the body

C2.1.6 Differences between transmembrane receptors in a plasma membrane and intracellular receptors in the cytoplasm or nucleus

• Intracellular receptors have hydrophilic amino acids → remain dissolved in aqueous fluids of the cytoplasm

• Transmembrane receptors have a band of hydrophobic amino acids on their surface + hydrophilic amino acids in contact with aq solutions inside and outside the cell

C2.1.7 Initiation of signal transduction pathways by receptors

• Steps of a signaling pathway (hydrophobic ligand)

  • ligand passes through membrane into cell

  • ligand binds to an intracellular receptor

  • ligand-receptor complex regulates gene expression

• Steps of a signaling pathway (hydrophilic ligand)

  • Ligand binds to transmembrane receptor (outside

  • Secondary messenger produced inside the cell by receptor

  • Secondary messenger activates effectors → carry out responses to the signal

  • First messenger: Extracellular ligand that binds to receptor

  • Second messenger: Small molecule inside the cell that transmits the signal

  • Signaling cascade: A series of chemical reactions that occur in response to a signal

• G-Protein Coupled Receptor (GPCR) Pathway

  • Ligand binds to GPCR → activates a G-protein (GDP → GTP)

  • G-protein activates effector enzymes → triggers cascade

  • second messengers amplify the signal

  • activation of protein kinases → cellular response

• Receptor Tyrosine Kinases (RTK) Receptor pathway

  • Ligand binds to RTK → dimerization of receptors

  • Receptor autophosphorylates

  • activates pathway

• Ion Channel Linked Receptor Pathway

  • Ligand binds to ion channel receptor

  • channel opens, ions flow in/out

  • Ion movement triggers secondary signaling cascade

C2.1.8 Transmembrane receptors for neurotransmitters and changes to membrane potential

• Neurotransmitters released into synaptic gap → diffuse into membrane of postsynaptic neuron/muscle fiber

  • bind to receptors (transmembrane proteins)

  • membrane channels open, ions movement

  • changes membrane potential

    • signal that stimulates/inhibits response

• Acetylcholine is one of the most common neurotransmitters

C2.1.9 Transmembrane receptors that activate G protein

• G-protein-couped receptors (GPCRs) convey signals using G-protein

• G-protein has 3 subunits ( alpha, beta, gamma)

  • GDP bound to alpha subunit in inactive state

• Ligand binds to receptor → changes shape → changes G-protein

  • GDP detaches from a subunit → GTP replaces it → activates G-protein

  • G-protein separates into its subunits and dissociates from receptor

  • Triggers cell’s response to signal

C2.1.10 Mechanism of action of epinephrine (adrenaline) receptors

• Epinephrine is secreted by adrenal glands

• Epinephrine binds to transmembrane receptor

  • activates G-protein

  • activates adenylyl cyclase

    • converts ATP in cytoplasm to cyclic AMP (cAMP)

  • cAMP is second messenger → amplifies signal

• Effects of epinephrine: physiological arousal

C2.1.11 Transmembrane receptors with tyrosine kinase activity

• Kinase: An enzyme that adds a phosphate group from ATP to a specific molecule (phosphorylation)

• Insulin is secreted by pancreas cells when blood glucose is high

• Insulin binds to receptors

  • two tails of protein bind to form a dimer

  • phosphorylates each other → triggers signal transduction

C2.1.12 Intracellular receptors that affect gene expression

• Steroid hormones directly pass through membrane

  • bind to intracellular receptors

  • hormone-receptor complex enters nucleus and attaches to DNA

  • changes gene expression → activates production of protein

• e.g. Testosterone + androgen receptor → production for FADS1 gene

Effects of the hormones estradiol and progesterone on target cells

• Estradiol and progesterone are steroid hormones

• Estradiol can stimulate or inhibit the release of Gonadotropin releasing hormone (GnRH) at different stages of the menstrual cycle

  • Estradriol binds to receptor → acts as transcription factor → enhancing transcription for GnRH mRNA

• Progesterone stimulates gene expression for insulin-like growth factor → maintain lining of endometrium

C2.1.14 Regulation of cell signaling pathways by positive and negative feedback

• Testosterone production is regulated by negative feedback