Unit 3: COMMUNICATION AND INTEGRATION AND HOMEOSTASIS

Question 1

List the 3 local cell-to-cell communication methods

Answer 1

1. gap junctions
2. contact dependent
3. paracrine and autocrine

Question 2

List the 2 long distance cell-to-cell communication methods

Answer 2

1. endocrine system
2. nervous system

Question 3

Gap junctions

Answer 3

Ø Recall: groups (connexons) of individual
proteins called connexins form fluid-filled
pores/channels between adjacent cells.
Cells are connected by a bridge of
cytoplasm.

Ø Each connexon is made of 6 connexin
monomers, 2 connexons (one from each
cell membrane) connect to for the
bridge/channel.

Ø Allows ions and small molecules to diffuse
directly from one cell to the next down
their concentration gradients (e.g. Ca++)

Ø Found in cardiac and smooth muscle
tissue, some neurons.

Question 4

Contact Dependent Signals

Answer 4

Ø Signal molecule (ligand) is not secreted but
is bound to the surface of the cell
membrane or is a protein that is part of the
extracellular matrix

Ø Ligand binds to a receptor in the
membrane of the adjacent cell - no
diffusion/transport of the signal molecule
through the ISF is necessary.

Ø Receptors are often cell adhesion molecules
(CAMs) which include integrins, selectins,
etc.

Ø Important signaling mechanism for the
immune system (e.g. antigen presentation)
and for development

Question 5

Paracrine and Autocrine Signals

Answer 5

Signal molecule (ligand) is secreted (released) into
the ECF

Ø Autocrine signals = ligand acts on cell that secreted it

Ø Paracrine Signal = ligand diffuses away from cell that
secreted it and acts on nearby cells

Ø E.g.1: Histamine (released by immune cells as part
of the inflammatory response) causes vasodilation
(increases blood flow to area causing redness).

Ø E.g.2: Eicosanoids – for example thromboxane is
released from blood clotting cells called platelets
and acts on smooth muscle cells in nearby blood
vessels to cause vasoconstriction (restricts blood
flow to prevent blood loss)

Question 6

Endocrine system

Answer 6

Ø Endocrine glands release chemical ligands called
hormones into the blood

Ø Hormones can travel through the circulation to act on
distant target cells in other parts of the body. Target
cells are those that have receptors for the hormone.
Cells that do not have a receptor for the hormone
cannot respond to the hormone.

Ø E.g.1: insulin secreted from the Islets of Langerhans in
the pancreas travels through the blood to act on
insulin receptors (which are a type of tyrosine kinase
receptor – see later notes) in liver cells and muscle
cells. Activation of these receptors by insulin causes
them to increase intake of glucose from the blood,
among other actions.

Question 7

Neurotransmitters

Answer 7

Ø Electrical signals travel a longer distance along a
neuron (nerve cell)

Ø At the end of the nerve cell, the electrical signal
causes the release of a chemical signal
(neurotransmitter) that travels a very short
distance to the target cell(s).

Ø Target cells can be other neurons or effector cells
(e.g. muscle cells or cells of an exocrine gland like
a sweat gland).
Ø E.g. Acetylcholine
Ø E.g.2: Epinephrine (adrenaline) and
norepinephrine (noradrenaline) released directly
from.a neuron
Ø E.g.3: GABA = gamma (𝛾)–aminobutyric acid.

Question 8

Neurohormones

Answer 8

Ø Electrical signals travel along a neuron (nerve
cell)

Ø At the end of the nerve cell, the electrical signal
causes the release of a chemical signal into the
blood (hormone) that travels a long distance to
a target cell(s).

Ø E.g.1: Releasing hormones from the
hypothalamus (like Growth Hormone releasing
Hormone, GHRH)
Ø E.g.2: Hormones released from adrenal
medulla – epinephrine (adrenaline) and
norepinephrine (noradrenaline)

Question 9

Explain the four features of all signal pathways

Answer 9

1. All signaling pathways used for cell-to-cell
   communication (except gap junctions) have 4 features:

a. Signal (ligand) – molecule often referred to as a first
messenger.

b. Receptor – activated by binding of the ligand and
initiates signal transduction.

c. Signal transduction – intracellular signaling pathways
resulting in modification of existing proteins or creation
of new proteins through transcription and translation.

d. Cellular response – change in activity of the cell resulting from changes in protein abundance/function

Question 10

What is a ligand?

Answer 10

signal molecules (chemicals) that bind to receptor
proteins on target cells in order to create (or prevent) a physiological response in the target cell.

Question 11

Ligands may be:

Answer 11

Lipophilic (= non-polar, hydrophobic) molecules – can cross the phospholipid bilayer and interact with protein receptors inside of the target cell .
ØE.g.1: thyroid hormone and steroid hormones like estrogen, testosterone,
cortisol – bind to receptors in the nucleus that regulate transcription
ØE.g.2: Nitric oxide (gas) – binds to and alters activity of intracellular enzymes
(plays a role in local blood vessel dilation)

ii. Lipophobic (= polar, hydrophilic) molecules – cannot cross the phospholipid bilayer and so must act on cell membrane receptors to trigger signal transduction pathways inside of the cell.

ØE.g.1: Neurotransmitters (like acetylcholine, norepinephrine, GABA)
ØE.g.2: Peptide Hormones including molecules like insulin & growth hormone.

ØNOTE: Eicosanoids, like prostaglandins/thomboxanes are lipophilic, but as ligands they bind to cell surface receptors (and so behave in a similar manner to lipohobic ligands).

Question 12

Receptors

Answer 12

protein receptors located inside of the cell (intracellular)
or in the cell membrane

Question 13

Describe,intracellular receptors

Answer 13

Ø Present in cytosol or in nucleus.
Ø Bind to lipophilic (hydrophobic) ligands.
Ø Alter gene expression to achieve cellular response = a slow process as new proteins must be made via transcription/translation. While response time is slow, changes in gene expression cause long lasting
effects.
Ø E.g. steroid hormone receptors

Question 14

Describe cellular receptors

Answer 14

Ø Present on surface of the cell membrane
Ø Bind to lipophobic (hydrophilic) ligands.
Ø Triggers intracellular signaling pathways (cascades)

Question 15

List the Four categories of Cell Membrane Receptors:

Answer 15

1) Chemically gated
(ligand gated ion channels);
2) G-protein coupled receptors (GPCRs);
3) Receptor-enzymes (e.g. tyrosine kinase);
4) Integrin receptors

Question 16

Signal transduction

Answer 16

converting one form of signal (e.g. ligand) into
another (e.g. the molecular events inside of a cell that will alter the
activity of the cell)

Question 17

Membrane receptors and their associated membrane proteins may:

Answer 17

1. Directly activate protein kinases (e.g. tyrosine kinase) that will phosphorylate (add a phosphate group to) existing intracellular proteins. Depending on the protein, phosphorylation may cause activation or deactivation of the protein, which will lead to a change in cellular activity (response).

Activate amplifier enzymes that will trigger the formation or release
of a “second messenger
igand does not enter cell, so membrane receptor triggers a
pathway that results in creation or release of an intracellular signal
(ion or molecule) that is able to act inside of the cell

Question 18

What can second messengers do?

Answer 18

1) Open or close gated ion channels.

2) Increase intracellular calcium levels

3) Alter activity of protein kinases or phosphatases (leading to phosphorylation or dephosphorylation of target proteins)

Question 19

List some common 2 messengers

Answer 19

Ø cAMP; cGMP; IP3 (inositol triphosphate); DAG (diacylglycerol);

Ca++ ions (enter into the cell through ion channels or are released from stores inside organelles like the endoplasmic reticulum)

Question 20

Describe the pathway involving intracellular receptors

Answer 20

a. Lipophilic ligand diffuses into cell from ISF

b. Ligand binds to and activates receptor in cytosol or nucleus
(if in cytosol, ligand-protein complex will then move into
nucleus).

c. Activated receptor complex in nucleus activates or inhibits gene transcription (DNA à mRNA) and translation (protein synthesis from mRNA template).

Ø If gene transcription is activated, more of the protein associated with the gene will be produced by ribosomes.
Ø If gene transcription is inhibited, less of the protein associated with the gene will be produced.
Ø Changes in cell function then relate to the abundance and function of the protein.

Question 21

Describe the pathway involving cell membrane receptors

Answer 21

ØSignal molecule (first messenger) does not enter cell, so must bind to receptor in cell membrane and trigger signal transduction

ØCan activate intracellular cascades (sequential activation of proteins) leading to production of second messengers and ultimately to a change in cell activity
ØCan be amplified – one signaling molecule

Question 22

Describe Receptor-channel (ligand gated ion channel) signaling

Answer 22

ØAlso called: neurotransmitter gated ion channels, chemically gated ion channels, or ionotropic receptors.

ØLigand is often a neurotransmitter.

ØBinding of ligand to a gated channel protein opens or closes the gates on a channel for a particular ion (e.g. Na+, K+, Cl-, Ca++).
This changes the permeability of the cell to the ion (opening the gate increases permeability, closing the gate decreases permeability).

ØWhen gate opens – rapid flow of an ion into or out of the cell down its concentration gradient creates an electrical signal that can activate voltage sensitive proteins (e.g. voltage gated ion channels in
the cell membrane) or trigger release of Ca++ from organelles.

ØSome gated ion channels may open in response to:
i) activation of a
GPCR; ii) a second messenger; iii) and electrical or mechanical
stimulus
ØFound mostly in nerve and muscle cells

Question 23

Describe integrin Receptor Pathways

Answer 23

ØIntegrins are transmembrane proteins (span the
whole membrane).

ØThe part of the protein that faces the ECF binds to
proteins in the extracellular matrix or to ligands
ØThe part of the protein exposed to the ICF is attached
to the cytoskeleton

ØWhen a ligand binds to the integrin receptor it
activates enzymes inside of the cell or makes changes
to the proteins that make up the cytoskeleton.
Depending on which proteins are affected, can allow
for movement of the cell (e.g. during phagocytosis or
when epithelial cells migrate during wound closure).
Also important for blood clotting as well as cell
growth and proliferation (stages of cell cycle)

Question 24

Describe Receptor-Enzyme Pathways

Answer 24

ØBinding of ligand to receptor on membrane facing
ECF directly activates an enzyme on the ICF facing
surface of the membrane.

ØReceptor and enzyme may be separate proteins or
may be different parts of the same protein (as in the
insulin receptor).

ØActivation of the enzyme directly results in
phosphorylation of intracellular proteins, altering
their function and creating a cellular response.
ØE.g1:. Tyrosine kinase receptors (phosphorylates
proteins)

Question 25

G-protein Coupled Receptor (GPCR) Pathways

Answer 25

ØMost signal transduction pathways use GPCRs

ØHundreds of known GPCRs.

ØGPCRs have 7 membrane spanning regions.

ØCalled “GPCRs because they bind to guanosine
triphosphate (GTP) and guanosine diphosphate (GDP).
Active form is bound to GTP, inactive form is bound to
GDP.
ØWhen ligands bind to GPCRs and activate them, one of
two things can happen:
i. The activated G-protein will open an ion channel,
or
ii. The activated G-protein will activate an amplifier
enzyme which will produce a second messenger

Question 26

Diagram and describe the mechanisms of: a) the G protein-coupled receptor (GPCR) adenylyl cyclase-cAMP system

Answer 26

1) Ligand binds to GPCR
Ø G-protein is activated (G-protein has 3 subunits, alpha,
beta and gamma. Each can have different actions)
Ø Activated GPCR can stimulate several G-proteins.

2) G-protein diffuses along cytosolic surface of cell membrane
to activate the amplifier enzyme protein adenylyl cyclase.
Each G- protein activates 1 adenylyl cyclase.

3) Adenylyl cyclase converts hundreds of ATP to cAMP (the second messenger). cAMP can diffuse throughout the cell.

4) cAMP activates a protein kinase called protein kinase A.

5) PKA diffuses throughout the cell and phosphorylates target
proteins, altering their function.
Ø Proteins with altered function alter the activity of the cell =
cellular response

Question 27

Diagram and describe the mechanisms of the GPCR phospholipase C

Answer 27

1) Ligand binds to GPCR and activates it.
Ø Activated GPCR activates G-protein.

2) G-protein diffuses along cytosolic
surface of cell membrane to activate
the amplifier enzyme protein
phospholipase C (PLC).

3) PLC breaks down membrane
phospholipids into 2 second messengers:

a) Diacylglycerol (DAG) – stays associated with the lipid in the membrane (it is a diglyceride)

b) Inositol triphosphate (IP3) – small polar molecule that diffuses throughout the cytoplasm.

4) DAG activates protein kinase C (PKC) which diffuses throughout the cell and phosphorylates
proteins. Phosphorylated proteins can change cell activity (cellular response).

5) IP3 binds to IP3 receptor on the endoplasmic reticulum (ER) and activates it. Activated IP3
receptor opens Ca++ channels on ER, allowing stores of Ca++ to be be released into
cytosol. Cytosolic Ca++ becomes another second messenger that can alter cell activity

Question 28

Specificity

Answer 28

receptor binds to only one type of or a
limited number of similar ligands. Only cells that
express the correct receptor can bind to the ligand
and initiate signal transduction. Cells without the
appropriate receptor for the ligand are unaffected

Question 29

Saturation

Answer 29

the degree to which receptors are
occupied by ligand. If all are occupied = 100%
saturation. Ability to respond to a signal is
limited by the number of receptors

Question 30

Agonists

Answer 30

a competing ligand (chemical
messenger) that binds to a receptor and triggers
the cells response. E.g. drugs that mimic the the
normal messengers action

Question 31

Antagonists

Answer 31

Competing ligands that bind and block
receptor activity. Prevents the actions of the natural
ligand

Question 32

Explain how signal pathways can be modulated by up-regulation and down-regulation.

Answer 32

Up-regulation = a increase in receptor number. May
occur in the presence of chronically low ECF levels of
ligand. Receptors are synthesized and moved to the
membrane. Increases sensitivity of cell to ligand and
helps to maintain a normal level of response.

Down-regulation = a decrease in receptor
number. Often occurs in the presence of
chronically high ECF levels of ligand. Receptors are
removed from membrane by endocytosis