What are the factors of direct contact between cells
Gap junctions
Cell-to-cell recognition
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Gap junctions
* cells are connected by tunnels formed by connexons * Allows ions and small water soluble chemicals to pass between cells * Cardiac and smooth muscle
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Cell-to-cell recognition
* interaction of cell-surface molecules
* Immune cells – recognize self vs. non-self
* Receptors meet glycocalyx
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How does cell communication occur through extracellular chemical messengers?
* Cells release ligands that bind to receptors on target cells to initiate a desired cellular response * Local regulators vs. Long distance regulators
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How does cell communication occur through local Regulators
Paracrine
Autocrine
Ex: histamine, cytokines, prostaglandins
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Paracrine
through diffusion, ligands affect cells in the **local** vicinity
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Autocrine
chemicals act on the cell that produced it
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Neurotransmitters
* secreted by neurons * Diffuse across the synaptic cleft and target the adjacent cell (neuron, gland, muscle) * Short-lived
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Long-range (distant) regulators
Hormones
Neurohormones
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Hormones
secreted into the blood by endocrine glands to travel to distant target cells
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Neurohormones
neurons secretes hormones into the blood
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How do hormones effect cells?
* Activate or inhibit enzymes * Direct protein synthesis through activation of transcription factors * Stimulate cell division * Alter membrane permeability – membrane potential or opening/closing of ion channels
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How do hormones work?
* chemical substances that travel through the blood to a target cell * Target cells must have specific receptors to which the hormone binds * These receptors may be intracellular or located on the plasma membrane
* They trigger a change in cellular activity
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Types of Hormones
Amines – amino acid derivatives
Peptides – proteins
Steroids – cholesterol based
Eicosanoids –derived from arachidonic acid (lipid)
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Transport of Hormones
Hydrophilic (water-soluble) hormones – dissolve in the plasma
Lipophilic (lipid-soluble) hormones – circulate bound to plasma proteins such as albumin
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Mechanism of Signaling Molecules
Lipid soluble hormones
Water soluble hormones
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Lipid soluble hormones
* Move through the plasma membrane and bind to an intracellular receptor in the nucleus
* Binding of the HRC to the DNA triggers transcription of a specific gene and the synthesis of a protein that initiates a cellular response
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Water soluble hormones
* **utilize a membrane bound receptor** * Binding of hormone causes a conformational change in the receptor
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Two affects of ligands binding to membrane bound receptors:
Triggers the opening or closing of ion channels or transfers the signal to a secondary messenger within the cell which triggers a cascade of biochemical events
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Types of Receptors
Ligand gated channel
Receptor enzyme
G protein coupled receptor
Integrin
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Ligand gated channel
Open or close the channel
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Receptor enzyme
Ligand binding to a receptor enzyme activates an intracellular enzyme
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G protein coupled receptor
Ligand binding to a G protein-coupled receptor opens an ion channel or alters enzyme activity
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Integrin
Ligand binding to integrin receptors alters the cytoskeleton
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Signal Transduction
* Amplifier enzyme activates several more molecules. * Protein Kinase transfers phosphate from ATP to protein. * Ca2+ binds to protein and alters the protein function.
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Secondary Messenger Pathways
**G-protein linked receptor**
**G proteins**
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G-protein linked receptor
* spans the membrane and is associated with a G protein on the cytoplasmic side * Ligand binds to the receptor * Receptor then activates a G protein
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G proteins
relay proteins that cycle between an inactive and active form
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Cyclic AMP Secondary Messenger Pathway steps 1-4
1. G protein activates the enzyme adenylate cyclase (amplifier) 2. Converts ATP to cyclic AMP 3. Activates protein kinase A which phosphorylates other proteins 4. Trigger cellular responses
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Calcium Secondary Messenger Pathway steps 1-2
1. Binding of ligand to a G protein linked receptor or a tyrosine kinase receptor
2\. Activates phospholipase C (amplifier) which cuts PIP2(phospholipid) to DAG and IP3
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Calcium Secondary Messenger Pathway steps 3-5
3. DAG will activate protein kinase C in another signaling pathway 4. IP3 binds to calcium channels triggering the release of calcium from the SER into the cytoplasm 5. Calcium binds to and activates calmodulin (protein) which can alter other proteins to bring about a cellular response