Gap junctions
Channels that connect adjacent cells (two adjacent cells express channel proteins called connexions); water filled pore: allows small molecules and ions to diffuse from one cell to the next; common in heart, smooth muscle and some neurons; cells are connected by cytoplasmic bridges; functional gap junction channel made from 2 connexon proteins (each connexon is made up of 6 connexin monomers; two connexons form a functional gap junction)
Contact-dependent signalling
A molecule (ligand) in the ECM of one cell binds to a receptor in the membrane of the adjacent cell; glycosylation (addition of carbs) of ligands plays a key role; immune system, development
Local communication
A signalling molecule is released (paracrine: signalling to cells in the immediate vicinity; autocrine: signalling to self)
Endocrine system
Secretes hormones; chemicals secreted into the blood that affect cells in other parts of the organism;
Neurotransmitters
An electrical signal travels distance along a nerve cell; causes release of a chemical; chemical travels across a small gap onto a target
Neurohormones
An electrical signal travels distance along a nerve cell; causes release of a chemical; chemical is released into the blood, and acts at distant targets
Except for gap junction signalling, cell-to-cell signalling requires what?
Signal (ligand); receptor; way to transduce the message (intracellular signalling pathways)
Signal transduction pathway
Signal molecule binds to receptor protein, activates intracellular signal molecules, alters target proteins to create a response
Intracellular receptors
Ligands are usually lipophilic (hydrophobic; eg. steroid hormones); able to diffuse through cell membrane and bind to receptors in the nucleus or cytosol; often alter gene expression (slow but long lasting)
Cell membrane receptors
Ligands are usually lipophobic (hydrophilic; eg. insulin); ligand does not diffuse through cell membrane; bind to membrane receptors; cause intracellular cascade; binding triggers “rapid” cellular responses
Integrin receptor
Integrin (receptor protein) binds ECM proteins (eg. collagen, laminin); binding ligand stimulates cell movement, growth, wound healing via cytoskeleton, changes in adhesion by changing interaction with ECM
Receptor channels
Ion channel; often called ligand-gated ion channels, neurotransmitter gated ion channels, and ionotropic receptors; endogenous ligand is often a neurotransmitter; when the ligand binds, the channel opens allowing a way for ions to enter and leave cells = electrical signal (synaptic transmission); allow Ca2+ into cells
Receptor enzyme
Activate amplifier enzymes; results in signal amplification (small amount of ligand creates large effect)
Tyrosine kinase receptor
Example of a receptor enzyme; transfers a phosphate group from ATP to tyrosine residue of a target protein
Explain the insulin receptor (eg. of TKR)
A complete insulin receptor contains the alpha receptor (containing the ligand binding domain) and the beta subunit (contains the transmembrane and the signalling domain)
1) Alpha subunits bind insulin
2) Binding of insulin causes receptors to dimerize and autophosphorylate; the beta subunit transmits the signal from the bound insulin to the cytoplasm
3) The dimerization and autophosphorylation activate a tyrosine kinase domain in the cytoplasm
4) Tyrosine kinase domains on the receptor phosphorylate target proteins including insulin receptor substrate, triggering other responses inside the cell
GPCRs
Hundreds of known ones; also called metabotropic receptors, 7 transmembrane domain receptor, and serpentine receptor; its activation leads to generation/release of second messengers
Second messenger
A signalling molecule synthesized or released by a cell in response to an extracellular signalling molecule; small, diffusible (can be hydrophobic or hydrophilic); stimulate a biological response
Explain the adenylyl cyclase pathway (eg. of GPCR)
1) Ligand binds to G protein receptor and activates the G protein; has 3 subunits (alpha, beta, gamma); once activated, the G protein can diffuse along the inside leaf of the membrane; activated receptor can stimulate several G-proteins
2) G protein diffuses along the inside of the membrane to activate the amplifier enzyme adenylyl cyclase; each G protein (Gs) activates one AC; G protein is modified by addition of fatty acid to make it stick to inner side of membrane
3) Adenylyl cyclase converts several hundred ATP into cAMP (second messenger, can diffuse through cell)
4) cAMP activates protein kinase A (PKA)
5) PKA diffuses within cell to phosphorylate many other proteins; many types can be phosphorylated, giving rise to complex cellular responses
Explain the phospholipase C pathway (eg. of GPCR)
1) Ligand binds to and activates G protein receptor (Gq)
2) G protein activates the phospholipase C; PLC acts on the phospholipid (PIP2)
3) PLC degrades membrane phospholipids (PIP2) into TWO second messengers: diaglycerol (DAG) and inositol tri-phosphate (IP3); DAG stays associated with the lips, IP3 is a small polar molecule that diffuses through the cytoplasm
4) DAG activates protein kinase C (PKC); PKC diffuses within the cell, and phosphorylates other proteins
5) IP3 binds to the IP3 receptor on the ER; activates IP3 receptor, allowed stored Ca2+ to be released into the cytoplasm; this Ca2+ becomes another second messenger
Explain calcium as a second messenger
1) Binds to the calcium-binding protein calmodulin to activate other proteins (including kinases)
2) Binds to motor proteins and allows action of cytoskeleton and motor proteins
3) Binds to synaptic proteins to trigger exocytosis/neurotransmitter release
4) Binds to ion channels to modulate their gating (Ca2+ gated ion channels)
5) In fertilized eggs, initiates development
NO (nitric oxide) as a second messenger
Synthesized by NO-synthase; an NO molecule has a half life of 2-30 seconds; synthesized by endothelial cells of arteries and neurons of PNS, and released at adjacent arterial smooth muscle; activates guanylyl cyclase, production of cGMP, activation of protein kinase G (PKG) leads to relaxation of smooth muscle
CO (carbon monoxide) as a second messenger
Can be useful in very small amounts; activates guanylyl cyclase
H2S (hydrogen sulfide) as a second messenger
Activates a number of protein kinases
Explain the arachidonic acid pathway (eg. of GPCR)
Similar to the PLC pathway; G proteins activate phospholipase A2 (PLA2); PLA2 degrades phospholipids into arachidonic acid; arachidonic acid are themselves second messengers and diffuse in and out of the cell and act as a ligand for GPCR cell membrane and adjacent cells
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Physiology and Control Systems11
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Molecules of Life37
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Membrane Dynamics38
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Communication31
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Resting Membrane Potential12
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CNS Intro and Action Potentials35
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Synaptic Transmission6
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Organization of the CNS0
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Sensory Processing0
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Visual Processing27
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Auditory and Vestibular Processing17
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Autonomic Nervous System15
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Skeletal Muscle40
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Cardiac Muscle13
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Endocrinology163
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Human Reproduction47
