Cellular Communication Types of Cell Signaling

CHAPTER Cellular Communication Types of Cell Signaling
3 §  Everything an animal does involves communication

among cells
§  Direct
§  Signaling cell and target cell connected by gap
Cell Signaling and §  Example: moving, digesting food junctions
Endocrine Regulation §  Signal passed directly from one cell to another
§  Cell signaling – communication between cells
§  Signaling cell sends a signal (usually a chemical) §  Indirect
§  Target cell receives the signal and responds to it §  Signaling cell releases chemical messenger
§  Chemical messenger carried in extracellular fluid
§  Some may be secreted into environment
§  Chemical messenger binds to a receptor on target cell
§  Activation of signal transduction pathway
PowerPoint® Lecture Slides prepared by
Stephen Gehnrich, Salisbury University
§  Response in target cell
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Indirect Signaling Over Short Distance Indirect Signaling Over Long Distance Types of Cell Signaling
§  Short distance Long distances

§  Paracrine §  Endocrine System
§  Chemical messenger diffuses to nearby cell §  Chemical messenger (hormone) transported by
§  Autocrine circulatory system
§  Chemical message diffuses back to signaling cell
§  Nervous System
§  Electrical signal travels along a neuron and chemical
messenger (neurotransmitter) is released
Figure 3.1
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
1
Direct Signaling Gap Junction Indirect Signaling
§  Gap junctions §  Three steps

§  Specialized protein complexes create an aqueous pore §  Release of chemical messenger from signaling cell
between adjacent cells (gland)
§  Movement of ions between cells §  Transport of messenger through extracellular
§  Changes in membrane potential environment to target cell
§  Chemical messengers can travel through the gap §  Communication of signal to target cell
junction §  Systems for indirect signaling have similarities and
§  Example: cAMP differences
§  Opening and closing of gap junction can be regulated
Figure 3.2
Glands Indirect Signaling Chemical Messengers
§  Six classes of chemical messengers

§  Peptides
§  Steroids
§  Amines
§  Lipids
§  Purines
§  Gases
§  Structure of chemical messenger (especially
hydrophilic vs. hydrophobic) affects signaling
mechanism
Figure 3.3 Table 3.1

2
Indirect Signaling Peptide/Protein Hormones Peptide/Protein Hormones
§  2-200 amino acids long §  Hydrophilic

§  Synthesized on the rough ER §  Soluble in aqueous solutions
§  Travel to target cell dissolved in extracellular fluid
§  Often as larger preprohormones
§  Bind to transmembrane receptors
§  Stored in vesicles
§  Signal transduction
§  Prohormones
§  Rapid effects on target cell
§  Secreted by exocytosis
Table 3.2
Synthesis & Secretion of Peptide Hormones Synthesis & Secretion of AVP Transmembrane Receptor
Figure 3.4 Figure 3.5 Figure 3.6

3
Steroid Hormones Synthesis of Steroid Hormones Steroid Hormones
§  Derived from cholesterol §  Hydrophobic

§  Synthesized by smooth ER or mitochondria §  Can diffuse through plasma membrane
§  Three classes of steroid hormones §  Cannot be stored in the cell
§  Mineralocorticoids §  Must be synthesized on demand
§  Electrolyte balance §  Transported to target cell by carrier proteins
§  Glucocorticoides §  Example: albumin
§  Stress hormones §  Bind to intracellular or transmembrane receptors
§  Reproductive hormones §  Slow effects on target cell (gene transcription)
§  Regulate sex-specific characteristics §  Stress hormone cortisol has rapid non-genomic effects
Figure 3.7
Steroid Hormones Amine Hormones Other Chemical Messengers
§  Chemicals that possess amine group (–NH2) §  Eicosanoids

§  Example: acetylcholine, catecholamines (dopamine, §  Most act as paracrines
norepinephrine, epinephrine), serotonin, melatonin, §  Hydrophobic
histamine, thyroid hormones §  Often involved in
§  Sometimes called biogenic amines inflammation and pain
§  Some true hormones, some neurotransmitters, some §  Example:
both prostaglandins,
leukotrienes
§  Most hydrophilic
§  Thyroid hormones are hydrophobic
§  Diverse effects
Figure 3.8 Figure 3.10

4
Other Chemical Messengers Communication to the Target Cell Ligand-Receptor Interactions
§  Gases §  Receptors on target cell §  Ligand-receptor interactions are specific
§  Most act as paracrines §  Hydrophilic messengers bind to transmembrane §  Only the correctly shaped ligand (natural ligand) can
§  Example: nitric oxide (NO), carbon monoxide receptor bind to the receptor
§  Purines §  Hydrophobic messengers bind to intracellular §  Ligand mimics
§  Function as neuromodulators and paracrines receptors §  Agonists – activate receptors
§  Example: adenosine, AMP, ATP, GTP §  Ligand §  Antagonists – block receptors
§  Chemical messenger that can bind to a specific §  Many ligand mimics act as drugs or poisons
receptor
§  Receptor changes shape when ligand binds
Ligand-Receptor Interactions Ligand-Receptor Interactions Ligand-Receptor Binding
§  A ligand may bind to more than one type of §  L + R ↔ L-R
receptor §  Formation of L-R complex causes response
§  Receptor isoforms §  More free ligand (L) or receptors (R) will increase the
§  Expressed on different target cells response
§  Different responses to the same ligand §  Law of mass action
§  A single cell may have receptors for many different §  Receptors can become saturated at high L
ligands §  Response is maximal
Figure 3.11
5
Ligand-Receptor Binding Changes in Number of Receptors Changes in Number of Receptors
§  Number of receptors affects number of L-R

complexes
§  More receptors à ↑ L-R complexes à ↑ response
§  Target cells can alter receptor number
§  Down-regulation
§  Target cell decreases the number of receptors
§  Often due to high concentration ligand
§  Up-regulation
§  Target cell increases the number of receptors
Figure 3.12 Figure 3.13a

Ligand-Receptor Dynamics Inactivation of Ligand-Receptor Complex Signal Transduction Pathways
§  Affinity of receptor §  L-R complex must be inactivated to allow §  Convert the change in receptor shape to an
for ligand affects responses to changing conditions intracellular response
number of §  Four components
L-R complexes §  Receiver
§  Higher affinity §  Ligand binding region of receptor
constant (Ka) à ↑ §  Transducer
response
§  Conformational change of the receptor
§  Amplifier
§  Increase number of molecules affected by signal
§  Responder
§  Molecular functions that change in response to signal
Figure 3.13b Figure 3.14

6
Transduction Pathway Types of Receptors Types of Receptors
§  Intracellular
§  Bind to hydrophobic ligands
§  Ligand-gated ion channels
§  Lead to changes in membrane potential
§  Receptor-enzymes
§  Lead to changes in intracellular enzyme activity
§  G-protein-coupled
§  Activation of membrane-bound G-proteins
§  Lead to changes in cell activities

Intracellular Receptors Intracellular Receptors Changes in Gene Transcription
§  Ligand diffuses across cell membrane

§  Binds to receptor in cytoplasm or nucleus
§  L-R complex binds to specific DNA sequences
§  Regulates the transcription of target genes
§  increases or decreases production of specific mRNA

7
Ligand-Gated Ion Channels Ligand-Gated Ion Channels Receptor Enzymes
§  Ligand binds to transmembrane receptor §  Ligand binds to transmembrane receptor
§  Receptor changes shape opening a channel §  Catalytic domain of receptor starts a
§  Ions diffuse across membrane phosphorylation cascade
§  Ions move “down” their electrochemical gradient §  Phosphorylation of specific intracellular proteins
§  Movement of ions changes membrane potential
Figure 3.19
Receptor Enzymes G-Protein-Coupled Receptors G-Protein-Coupled Receptors
§  Ligand binds to transmembrane receptor

§  Receptor interacts with intracellular G-proteins
§  Named for their ability to bind guanosine nucleotides
§  Subunits of G-protein dissociate
§  Some subunits activate ion channels
§  Changes in membrane potential
§  Changes in intracellular ion concentrations
§  Some subunits activate amplifier enzymes
§  Formation of second messengers

8
Second Messengers Inositol-Phospholipid Signaling Cyclic-AMP Signaling
Table 3.3 Figure 3.26 Figure 3.27

Interaction Among Transduction Pathways Regulation of Cell Signaling Regulation of Cell Signaling
§  Cells have receptors for different ligands §  Cell signaling is important for regulation of §  Set Point
§  Different ligands activate different transduction physiological processes §  The value of the variable that the body is trying to
pathways §  Components of biological control systems maintain
§  Response of the cell depends upon the complex §  Sensor §  Feedback loops
interaction of signaling pathways §  Detects the level of a regulated variable §  Positive
§  Sends signal to an integrating center §  Output of effector amplifies variable away from the set
§  Integrating center point
§  Evaluates input from sensor §  Positive feedback loops are not common in physiological
systems
§  Sends signal to effector
§  Negative
§  Effector
§  Output of effector brings variable back to the set point
§  Target tissue that responds to signal from integrating
center
9
Feedback Regulation Pituitary Hormones Posterior Pituitary
§  Pituitary gland secretes many hormones §  Extension of the hypothalamus
§  Two distinct anatomic sections: §  Neurons that originate in hypothalamus terminate in
§  Anterior pituitary (adenohypophysis) posterior pituitary
§  Posterior pituitary (neurohypophysis) §  Neurohormones oxytocin and vasopressin synthesized
in cell body and travel in vesicles down axons
§  First-order endocrine pathway
§  Hypothalamus receives sensory input
§  Hypothalamus serves as integrating center
Figure 3.28
Posterior Pituitary Anterior Pituitary Anterior Pituitary
Hypothalamus synthesizes and secretes

neurohormones
↓
Hypothalamic-pituitary portal system
↓
Anterior pituitary releases hormones
§  Tropic hormones
§  Cause release of another hormone
§  Third-order endocrine pathway

10
Hypothalamus and Anterior Pituitary Regulation of Blood Glucose Regulation of Blood Glucose
§  Precisely controlled §  Insulin and glucagon are secreted by pancreas
§  Blood glucose too low, brain cannot function §  Direct feedback loops
§  Blood glucose too high, osmotic balance of blood §  Pancreas also receives neural and hormonal signals
disturbed §  Antagonistic pairing
§  Hormones §  Hormones that have opposing effects
§  Insulin lowers blood glucose levels
§  Glucagon raises blood glucose levels
Figure 3.31
Pathways Regulating Insulin Secretion Antagonistic Regulation of Blood Glucose Additivity and Synergism
§  Additivity
§  When hormones cause same response in a target cell
§  Hormones do not use the same signaling pathway
§  Example: glucagon, epinephrine, and cortisol all raise
blood glucose by different mechanisms
§  Response of target cell to combinations of these
hormones is additive
§  Synergism
§  When hormones enhance affect of other hormones
§  Response of target cell to combinations of these
hormones more than additive

11
Additivity and Synergism Control of Glucose Levels in Arthropods Vertebrate Stress Response
§  Crustacean §  Interaction between nervous and endocrine systems

hyperglycemic §  Sense organs detect “stress”
hormone (CHH) §  Activation of sympathetic nerves
§  Neurohormone from §  Increased heart rate, respiration, dilation of airways
crab eyestalk §  Decreased secretion of insulin from pancreas
§  Secreted in response §  Increased secretion of glucagon from pancreas
to low glucose in §  Increased secretion of epinephrine from adrenal medulla
blood/hemolymph §  Increase in blood glucose level

Vertebrate Stress Response Vertebrate Stress Response Adrenal Tissue in Different Vertebrates
Hypothalamic-pituitary axis stimulates the adrenal

cortex
§  Hypothalamus
§  Secretes corticotropin-releasing hormone (CRH)
§  Anterior pituitary
§  Secretes adrenocorticotropic hormone (ACTH)
§  Adrenal cortex
§  Secretes cortisol
§  Stimulates target cells to increase blood glucose level

12
Evolution of Cell Signaling Vertebrate Hormones Vertebrate Hormones
§  Endocrine systems of animals diverse §  Evolutionary changes in way tissues respond to a
§  Suggests multiple evolutionary origins hormone, rather than a change in hormone
molecules
§  Chemical messengers, receptors, and cell signaling
§  Some hormones have same affect in different
mechanisms of animals share many similarities
animals
§  Suggests a common ancestor §  Example: human growth hormone increase growth
rate in fish; estrogen from pregnant mares can be used
in post-menopausal women
§  Some hormones have a different affect in different
animals
§  Example: prolactin stimulates milk production in
mammals, inhibits metamorphosis and promotes
growth in amphibians, regulates water balance in fish
Table 3.3
13

Cellular Communication Types of Cell Signaling

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CHAPTER Cellular Communication Types of Cell Signaling

3 § Everything an animal does involves communication

§ Short distance Long distances

§ Gap junctions § Three steps

Glands Indirect Signaling Chemical Messengers

§ Six classes of chemical messengers

Figure 3.3 Table 3.1

§ 2-200 amino acids long § Hydrophilic

Figure 3.4 Figure 3.5 Figure 3.6

§ Derived from cholesterol § Hydrophobic

Steroid Hormones Amine Hormones Other Chemical Messengers

§ Chemicals that possess amine group (–NH2) § Eicosanoids

Figure 3.8 Figure 3.10

Ligand-Receptor Interactions Ligand-Receptor Interactions Ligand-Receptor Binding

§ Number of receptors affects number of L-R

Figure 3.12 Figure 3.13a

Ligand-Receptor Dynamics Inactivation of Ligand-Receptor Complex Signal Transduction Pathways

Figure 3.13b Figure 3.14

Figure 3.15 Figure 3.16

Intracellular Receptors Intracellular Receptors Changes in Gene Transcription

§ Ligand diffuses across cell membrane

Figure 3.17 Figure 3.18

Receptor Enzymes G-Protein-Coupled Receptors G-Protein-Coupled Receptors

§ Ligand binds to transmembrane receptor

Figure 3.20 Figure 3.25

Table 3.3 Figure 3.26 Figure 3.27

Posterior Pituitary Anterior Pituitary Anterior Pituitary

Hypothalamus synthesizes and secretes

Figure 3.29 Figure 3.30

Figure 3.33 Figure 3.34

§ Crustacean § Interaction between nervous and endocrine systems

Figure 3.35 Figure 3.36

Hypothalamic-pituitary axis stimulates the adrenal

Figure 3.37 Figure 3.38

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3 §  Everything an animal does involves communication

§  Short distance Long distances

§  Gap junctions §  Three steps

§  Six classes of chemical messengers

§  2-200 amino acids long §  Hydrophilic

§  Derived from cholesterol §  Hydrophobic

§  Chemicals that possess amine group (–NH2) §  Eicosanoids

§  Number of receptors affects number of L-R

§  Ligand diffuses across cell membrane

§  Ligand binds to transmembrane receptor

§  Crustacean §  Interaction between nervous and endocrine systems