Communication and Integration

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Communication and Integration
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Methods of Cell to Cell Communication

• Direct transfer
• Gap junctions
• Contact-dependent signals
• Cell adhesion molecules
• Local chemical communication
• Paracrine
• Autocrine
• Long distance communication
• Electrical
• Chemical (Endocrine)

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Signal Pathways

• Common features
• Ligand binds to receptor
• Ligand binding activates receptor
• Intracellular molecules activated
• Last signal molecule
• Initiates synthesis of target protein
• Modifies target protein
• RESPONSE

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Signal Pathways

• Receptors
• Bind ligand
• Signal transduction
• Receptor locations
• Nucleus
• Cytosol
• Cell membrane
• Lipophobic (hydrophilic) ligands

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Categories of Membrane Receptors and Effectors

• Ligand-gated channels
• Integrins linked to cytoskeleton
• Receptor-enzymes
• G protein-coupled receptors

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Ligand Gated Channels

• Simplest Receptors
• Binding to receptor opens/closes channel gate
• Non-receptor ligand gated ion channels
• Second messenger linked ion channels
• cAMP
• Membrane effectors
• G proteins

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Integrin Receptors

• Integrins
• Membrane spanning proteins
• Bind to ECM or ligands (extracellular)
• Ligand binding
• Activates intracellular enzymes
• OR
• Alters cytoskeleton organization

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Receptor Enzymes

• Receptors on extracellular side, enzymes on
  intracellular side
• Enzymes
• Protein kinases
• Tyrosine kinase
• Guanylyl cyclase (GTP?cGMP)
• Ligands
• Growth factors
• Cytokines
• Insulin

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G Protein Coupled Systems

• Activation of ion channels
• G proteins linked to amplifier enzymes
• Adenylate cyclase
• ATP?cAMP
• cAMP?protein kinase A
• Guanylate cyclase
• GTP?cGMP
• cGMP?Phosphodiesterase
• Phospholipase C
• Phospholipase C?DAG IP3

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Calcium

• Ionic messenger
• Extracellular calcium enters when channels open
• Intracellular calcium stored in ER
• Calcium dependent event
• Binding to calmodulin
• Binding to other regulatory proteins
• Movement of contractile proteins
• Exocytosis
• Binding to ion channels
• Embryo development

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Nitric Oxide and Carbon Monoxide

• Soluble gases
• Paracrine action
• NO synthesized by nitric oxide synthase
• Activates guanylyl cyclase resulting in cGMP
  formation
• NO actions
• Brain neurotransmitter, neuromodulator
• Blood vessels - vasodilation

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Lipid Messengers

• Products of arachidonic acid
• Leukotrienes
• Produced by lipoxygenase
• Airway smooth muscle constriction
• Anaphylaxis
• Prostanoids
• Produced by cycloxygenases (COX1, COX2)
• Prostaglandins, thromboxanes
• Inflammation, sleep, pain, fever

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Signal Modulation

• Saturation, Specificity and Competition
• Agonist
• Mimic normal ligand
• Bind to and activate receptor
• Antagonist
• Oppose action of ligand
• Bind to and block receptor

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Multiple Receptors

• Receptor isoforms
• Variants with similar binding properties BUT
  differing cellular response
• Cellular response depends on specific isoform NOT
  on ligand

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Up and Down Regulation

• Saturation
• Fixed number of receptors
• Down regulation
• Number of receptors decreases
• OR
• Binding affinity of receptor decreases
• Up regulation
• Number of receptors increases

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Signal Termination

• First messenger degraded by enzymes in
  extracellular fluid
• Removal of first messenger by transporting into
  cells
• Ligand-receptor complex can be endocytosed and
  degraded

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Homeostasis

• Tonic Control
• Antagonistic Control
• Local Control
• Localized change and response
• Paracrine or autocrine
• Reflex Control
• Long distance reflex control pathways
• Nervous, endocrine or cytokine
• Response loop
• Input?Integration?Output

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Response Loop

• Stimulus
• Sensory receptor
• Specialized cells or parts of cells
• Minimum threshold
• Afferent pathway?Integrating center?
• Efferent pathway
• Effectors
• Cells that carry out the response( must have
  proper receptor)
• Muscles, glands
• Response

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Modulating the Response Loop

• Setpoints
• Negative feedback loops
• Opposes original signal
• Homeostatic
• Positive feedback loops
• Reinforces original signal
• Feedforward control
• Reflex that anticipates change

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Biological Rhythms

• Circadian rhythm
• Diurnal
• Nocturnal
• Seasonal rhythm

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Comparison of Nervous and Endocrine Systems

• Specificity
• Nervous Specific target cell
• Endocrine Less specific target but receptors
  specific
• Nature of signal
• Nervous Electrical and chemical
• Endocrine Hormonal (chemical)
• Speed
• Nervous faster than endocrine

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Comparison of Nervous and Endocrine Systems

• Duration of Action
• Nervous shorter duration than endocrine
• Short term function nervous
• Long term function endocrine
• Coding for stimulus intensity
• Nervous frequency of impulses
• Endocrine hormone concentration

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Pathways

• Endocrine reflexes
• Endocrine cells act as receptors and integrating
  centers (no afferent path)
• Efferent pathway is the hormone
• Nervous reflexes
• Receptor stimulated
• Afferent neuron to integrating center
• Efferent neuron to target
• Neuroendocrine
• Receptor stimulated
• Afferent neuron to integrating center
• Efferent neuron releases neurohormone into blood

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