Anatomy & Physiology 34A Lecture
Chapter 3 – Cell Communication and Homeostasis
I. Overview
A. Cell-to-Cell Communication
B. Signal Pathways
C. Cell Membrane Receptors
D. Novel Signal Molecules
E. Modulation of Signal Pathways
F. Control Pathways: Response & Feedback Loops
II. Cell-to-Cell Communication
A. The two basic methods of physiological communication (signals)
are chemical and electrical
1. Electrical signals are changes in a cell’s membrane potential
(voltage) via the flow of ions, as occurs in nerve impulses
2. Chemical signals result from cells secreting chemicals (e.g.,
hormones and neurotransmitters) into the extracellular space and
blood stream
3. Cells that receive electrical or chemical signals are target cells
B. Four types of cell-to-cell communication are
1. Direct cytoplasmic transfer of signals through gap junctions
2. Contact-dependent signaling – surface molecules of one cell
bind to surface molecules of another cell
3. Local chemical communication by chemicals that diffuse
through the extracellular fluid
4. Long distance communication via both electrical signals from
nerve cells and chemical signals in the blood stream
C. Gap Junctions transfer chemical and electrical signals
1. Gap junctions are protein channels between adjacent cells
2. When open, gap junctions allow ions and small molecules to
diffuse from cell to cell
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3. Gap junctions are found between many cells, including cardiac
and smooth muscle cells, and some neurons
D. Contact-dependent signals require cell-to-cell contact
1. Direct cell-to-cell contact signaling occurs in the immune system,
and during growth and development
2. Cell Adhesion Molecules (CAMs) bind some cells together and
participate in cell-to-cell signaling
E. Paracrines & Autocrines are local chemical signals distributed by
diffusion
1. Paracrines are chemicals (e.g., histamine) secreted into the
interstitial fluid in the extracellular space, and diffuse to nearby
target cells
2. Autocrines are chemicals that act on the same cell that secreted
the chemical
F. Electrical signals, Horomones, & Neurohormones carry out long
distance communication
1. Endocrine gland cells secrete chemical messengers called
hormones into the blood stream
a. Hormones travel in the blood stream to their target cells
b. Target cells have specific receptors for the hormones
2. The nervous system uses both chemical and electrical signals
a. Electrical signals travel to the end of a neuron and trigger the
release of a chemical signal (neurocrine) to a target cell
b. Neurocrines may be
1) Neurotransmitters – fast acting chemical secreted across a
gap between the neuron and its target cell
2) Neuromodulators – slow acting paracrine or autocrine
chemicals
3) Neurohormones – chemicals secreted into the blood
stream
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III. Signal Pathways
A. All signal pathways share these common features
1. A signal molecule (ligand, or 1st messenger) binds to its receptor.
2. Ligand binding activates the receptor
3. The receptor activates intracellular signal molecules (2nd
messengers)
4. The last signal molecule in the pathway either
a. Modifies a target protein to create a response
b. Initiates synthesis of a target protein
B. Receptors are located inside the cell or in the cell membrane
1. Target cell receptors are found in the nucleus, the cytosol, or in
cell membranes
2. Chemical signal molecules are either water soluble (hydrophilic)
or lipid soluble (hydrophobic)
a. Water soluble signals (e.g., peptide hormones) bind to
receptors on the target cell membrane and trigger an
intracellular response
b. Lipid soluble signals (e.g., steroid hormones) usually diffuse
through the target cell membrane and bind to cytoplasmic or
nuclear receptors
1) Receptor activation often turns on or off a gene that directs
protein synthesis
C. Membrane proteins facilitate signal transduction
1. Signal transduction is the transmission of information from one
side of the membrane to another via membrane proteins
2. Signal transduction pathways use membrane proteins and
intracellular 2nd messengers to produce an intracellular response
a. A signal molecule binds to and activates a membrane receptor
b. Some pathways activate protein kinases that transfer a
phosphate from ATP to a protein (i.e., phosphorylation)
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c. Other pathways activate amplifier enzymes (e.g., adenylyl and
guanylyl cyclase) that create 2nd messenger molecules (e.g.,
Ca2+, cAMP, cGMP)
d. 2nd messengers, in turn can
1) Open or close ion channels, which creates electrical signals
2) Increase intracellular calcium levels
3) Change enzyme activity, especially in kinases
(phosphorylators) and phosphatases (dephosphorylators)
e. Proteins modified by calcium binding and phosphorylation
control
1) Metabolic enzymes
2) Motor proteins for muscle contraction and cytoskeletal
movement
3) Proteins that regulate gene activity and protein synthesis
4) Membrane transport and receptor proteins
f. A signal transduction pathway is a cascade that begins when a
stimulus (signal molecule) activates another molecule, which
activates another, etc., until a product is eventually formed
IV. Cell Membrane Receptors include receptor enzymes, G proteinlinked, integrin, and ligand gated receptors
A. Receptor-enzymes have protein kinase or guanylyl cyclase activity
1. Receptor enzymes have receptors on the extracellular side of the
membrane that activate enzymes in the intracellular side
2. Receptor kinases (e.g., the insulin tyrosine kinase receptor)
transfer phosphates from ATP to a protein
3. Guanylyl cyclase converts GTP to cyclic GMP (cGMP), a
second messenger
4. Ligands for receptor enzymes include growth factors, cytokines,
and the hormone insulin
B. Most signal transduction uses G proteins
1. G protein-coupled receptors span the cell membrane, and are
linked to a G protein on the cytoplasmic side
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2. Ligands that bind to these receptors include hormones, growth
factors, and neurotransmitters
3. Ligand binding causes the G protein to exchange GDP for GTP,
thus activating the G protein
4. An active G protein can either
a. Open an ion channel in the membrane, or
b. Alter enzyme activity on the cytoplasmic side
C. G Protein-coupled Adenylyl cyclase-cAMP is the signal
transduction system for many water soluble hormones
1. Adenylyl cyclase is a membrane enzyme that converts ATP to
the 2nd messenger cyclic AMP (cAMP)
2. cAMP activates protein kinase A, which phosphorylates other
proteins
D. G protein-linked receptors also use lipid-derived 2nd messengers
1. Ligand binding activates phospholipase C (PL-C)
2. PL-C converts a membrane phospholipid into 2 2nd messengers –
diacylglycerol (DAG) and inositol triphosphate (IP3)
a. DAG interacts in the membrane with protein kinase C, which
phosphorylates cytosolic proteins
b. IP3 enters the cytoplasm and binds to a calcium channel on the
ER, which opens the channel and allows Ca2+ to diffuse out
E. Integrin receptors transfer information from the ECM
1. Integrins are integral proteins that mediate blood clotting, wound
repair, and other immune functions
2. Ligands include antibodies and blood clotting molecules
3. Integrins attach to the cytoskeleton, and ligand binding can
activate intracellular enzymes or alter cytoskeletal organization
4. Genetic defects in integrin proteins can result in defective WBCs
and platelets
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F. Ligand-gated ion channels initiate rapid intracellular responses via
electrical impulses
1. These channels are found in nerve and muscle cell membranes
2. When a ligand (e.g., acetylcholine) binds, it opens or closes the
ion channel, altering the membrane’s electrical potential
V. Novel Signal Molecules
A. Calcium is an important intracellular signal
1. Calcium enters the cytosol from
a. Extracellular fluid via Ca2+ channels, or
b. Intracellular compartments (e.g., ER), released by 2nd
messengers, such as IP3
2. Once in the cytosol, Ca2+ affects cell activity by binding to
a. Calmodulin protein, which alters enzyme activity or the open
state of ion channels
b. Regulatory proteins that alter movement of contractile proteins
(e.g., troponin) or cytoskeletal proteins (e.g., microtubules)
c. Other regulatory proteins that trigger exocytosis of secretory
vesicles (as in insulin secretion)
d. Ion channels, to alter their open state (e.g., Ca2+ activated K+
channel of nerve cells)
B. Gases are short-lived signal molecules
1. Nitric oxide (NO) is an autocrine/paracrine gas formed from the
amino acid arginine and oxygen
a. NO diffuses into target cells and activates guanylyl cyclase,
which in turn forms the 2nd messenger cGMP
b. In the brain, NO acts as a neurotransmitter
c. Blood vessel endothelial cells produce NO, which relaxes
adjacent smooth muscle cells, causing vasodilation
2. Carbon monoxide (CO) is produced in minute amounts, and has
an action similar to NO.
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VI. Modulation of Signal Pathways
A. Receptors exhibit saturation, specificity, and competion
1. Like enzymes, each receptor binds to a specific molecule (ligand)
or related molecule.
2. The response may be agonistic or antagonistic
a. Agonists are ligands that activate receptors
b. Antagonists are competitors that block receptor activity
3. Different forms of a receptor (isoforms) can bind the same ligand
and have different effects (e.g., epinephrine can bind to α & β
adrenergic receptors)
B. Up- and Down-Regulation of receptors enables cells to modulate
cellular response
1. Down-regulation is a decrease in a cell’s number of receptors or
their binding affinity, often in response to high ligand
concentrations (e.g., high insulin concentrations cause a downregulation of insulin receptors in type II diabetes)
2. Up-regulation is an increase in a cell’s number of receptors,
often in response to low ligand concentrations, which increases
the cell’s sensitivity to the ligand
C. Cells have mechanisms for terminating signal pathways, such as
1. Removing the signal molecule, or
2. Breaking down the receptor-ligand complex
D. Pharmacologists investigate signaling mechanisms to design drugs
to treat disease. Examples of signal blockers are
1. Calcium channel blockers to treat high blood pressure
2. SERMs for treating estrogen-dependent cancers
3. COX2 inhibitors that prevent the formation of inflammatory
prostaglandins
VIII. Control Pathways: Response and Feedback Loops
A. Homeostatic responses have 3 components
1. A stimulus or change in a regulated variable
2. A cell or tissue that evaluates the stimulus and initiates a
response
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3. Cells or tissues that carry out the response
B. Homeostasis may be maintained by local or long-distance
pathways
1. Local pathways include paracrine and autocrine responses
2. Long distance responses include reflex control pathways, which
consist of response loops that begin with a stimulus and end with
a response
a. Stimulus or change is perceived by a
b. Receptor (e.g., sensory neuron) that sends out an
c. Input (afferent) Signal to an
d. Integration center that evaluates the incoming signal,
compares it to a setpoint, then sends an
e. Output (efferent) signal (e.g., nerve impulse or hormone) to an
f. Effector (target cell or tissue) that carries out a
g. Response to restore homeostasis
D. Negative and positive feedback loops modulate the response loop
1. Negative feedback is when a change is sensed and a response is
initiated to reverse the change and restore homeostasis
2. Positive feedback is when a change is sensed and a response is
sent to reinforce the change (e.g., hormonal control of uterine
contractions during childbirth)