In This Lesson:
Cell
Communication
and the
Endocrine System
(Lesson 5 of 5)
Today is Tuesday,
October 27th, 2015
Pre-Class:
What is/are the female hormone(s)?
What is/are the male hormone(s)?
Guided readings should be on your desks.
Today’s Agenda
• Biostatistics: Standard Error and Standard
Deviation
• Cell Communication
– AKA membrane function in like…super detail.
• Hormones and the Endocrine System
• Where is this in my book?
– Chapters 11 and 45
By the end of this lesson…
• You should be able to calculate standard
deviation and standard error for a set of data.
• You should be able to describe the G proteincoupled receptor, receptor tyrosine-kinase, and
intracellular receptor mechanisms of cell
communication.
• You should know how hormones work.
• You should be able to explain feedback loops and
how they function to maintain homeostasis.
Biostatistics
• Part of AP Biology is learning how to do the statistical
analyses necessary to validate the results of an experiment.
• The Chi-Squared Analysis was part of our Animal Behavior
lesson, although it doesn’t really have anything to do with
animal behavior directly.
• Today we learn Standard Error and Standard Deviation,
even though they don’t really have anything to do with cell
communication.
– Or the endocrine system.
• Fact Sheet – Unit 3 – Standard Deviation and Standard
Error Tutorial
Cell Communication
• So far nearly everything we’ve done has been
about the cell in isolation.
– Except for maybe the junctions between cells.
• In reality, unless you’re unicellular, your cells
need to communicate with one another.
– Actually, even being unicellular doesn’t excuse you
from the need to communicate.
– Even yeast cells actually have two sexes (a and α) that
mate – a process which requires its fair share of
communication.
– For more: TED: Bonnie Bassler – How Bacteria Talk
Communication Modes
• Cells actually can respond to light and touch, in
addition to the usual chemical signals.
– We’re talking chemical signals right now.
• The general chemical signaling process leads to what’s
known as a signal transduction pathway.
– This sounds fancy, but it really just means that a stimulus (a
signal) is received by the cell and changed into a response
(is transduced) through a series of molecules (a pathway).
• Signal transduction pathways are remarkably similar
across a wide range of organisms, suggesting they’ve
been around awhile.
Communication Ranges
• Think for a second how you might communicate with
someone else.
– How would you communicate if you were in the same
room?
– How would you communicate if you were in different
states?
• Consider also how you would communicate in light of
the speed necessary to do so.
– Needing to deliver something urgently might change your
decision over how to deliver it.
• In the same way:
– Electrical signaling (nerves) = fast, urgent communication.
– Chemical signaling (molecules) = gradual communication.
Cell Communication
• Local Signaling:
– Paracrine Signaling:
when a signal affects a
neighboring cell.
– Synaptic Signaling:
paracrine signaling in
neurons – the end of one
nerve cell releases
neurotransmitter into the
synapse (space between
neurons) to signal the
next.
Cell Communication
• Long Distance Signaling:
– Hormones travel through
blood in animals; through
plasmodesmata in plants.
– Plant hormones may also
diffuse through the air.
• Ethylene gas – the stuff that
comes from a ripening fruit – is
an example of an air hormone.
The Signal Transduction Pathway
Three Steps
• Step 1: Reception:
– The cell needs to receive a chemical signal (a ligand).
• A ligand is any small molecule that binds to a larger one.
• The larger molecule is usually a receptor protein.
The Signal Transduction Pathway
Three Steps
• Step 2: Transduction
– The membrane receptor protein then activates one or more
other molecules to carry the signal deeper into the cell.
– These other molecules are called relay molecules and may
be involved in a phosphorylation cascade (more later).
The Signal Transduction Pathway
Three Steps
• Step 3: Response
– The cell does something.
– This could be the activation of a gene, change in the
cytoskeleton, activity of an enzyme, or just about
anything else.
Signal Transduction Pathways
• If it helps, think of signal transduction pathways like
what happens when you get a text message:
– Reception = Your phone vibrates or dings.
– Transduction = You unlock the phone and read the
message.
– Response = You write back, smile, cry, or throw the
phone against the wall.
Key Enzymes in Signal Transduction
• Before we look at the individual signal transduction forms,
keep in mind the following two types of enzymes and their
jobs:
– Protein Kinase – a kinase removes phosphate groups from
(dephosphorylates) ATP and adds them to (phosphorylates) a
protein.
– Protein Phosphatases – a phosphatase takes the phosphate back
from the protein.
• These may act in a phosphorylation cascade to make a
response.
– A phosphorylation cascade is just a lot of
phosphorylation/dephosphorylation and is associated with the
“transduction” step of cell communication.
– It also helps in amplification – more later.
Phosphorylation Cascade
Examples of
Signal Transduction Pathways
• A signal transduction pathway can be
“achieved” through one of these four total
methods:
– Intracellular Receptors
– Extracellular (Cell Surface Transmembrane)
Receptors
1. G Protein-Coupled Receptors
2. Tyrosine-Kinase Receptors
3. Ion Channel Receptors
Intracellular Receptors
• This is when a signal molecule, still
called a ligand, enters a cell to elicit
a response.
• Inside the cell, it binds to a
receptor protein in the cytoplasm
and then can affect transcription or
other cell activities.
– In this case, we could call the
ligand/receptor complex a
transcription factor.
• Onto the extracellular receptors!
1. G Protein-Coupled Receptor
• G proteins are guanine
nucleotide-binding proteins.
• So, a G protein-coupled receptor
(GPCR) is a membrane receptor
that is linked in some way to a G
protein.
– There’s the G protein and there’s
the receptor (they’re different).
• G protein-linked receptors have
seven α helices spanning the
membrane.
• These receptors are responsible
for relaying a signal from a ligand
to the interior of the cell (NOT
relaying the ligand itself).
Energy Molecules
• Before we launch into how a G protein-coupled
receptor works, we need to look into a molecule
that powers the G protein.
• What am I talking about?
• No, not ATP…GTP!
– ATP = Adenosine triphosphate
– GTP = Guanosine triphosphate
• Key: Each is a nucleotide with THREE phosphate
groups.
• Key: When “used up,” the molecule is reduced
to TWO phosphate groups, known as
adenosine/guanosine diphosphate.
ATP vs. GTP
• They’re similar, but different in the same way
that adenine and guanine are different.
– Adenosine = adenine (a nitrogenous base) + ribose
– Guanosine = guanine (a nitrogenous base) + ribose
• ATP is the more familiar energy “currency” of
the cell, but GTP plays a role too.
– The key is not so much the “adenosine” or
“guanosine” part as is the “triphosphate” part.
– The bonds between the phosphate groups contain
the energy.
Back to G Protein-Coupled Receptors
• Inactive:
– The receptor is spanning the membrane.
– The G protein is bound to GDP and stuck to the inner membrane.
– An enzyme also exists on the inner surface of the cell membrane.
Back to G Protein-Coupled Receptors
• Activation:
– The orange ligand activates the GPCR, changing its tertiary
structure, which bonds to the G protein.
– GTP replaces GDP, and the G protein moves to the enzyme.
– The enzyme prompts the next cellular responses.
G Protein Activation In Depth
• The G protein is actually made of three subunits,
making it a trimer:
– Gα, Gβ, and Gγ.
• That’s G (alpha), G (beta), and G (gamma).
• When the G protein is activated, it dissociates
into two parts:
– Gα (this has the GTP attached)
– Gβ/Gγ complex
• Both pieces are capable of activating various
other pathways.
G Proteins
• For a mental image…
– Bat G-Protein video
– Think of the Bat-Pod like a Gα subunit (and it’s got the
GTP, like Batman, attached to it).
– Think of the rest of the Batmobile like the Gβ/Gγ
complex.
• Except Gβ/Gγ complexes don’t normally explode.
• Overall Metaphor:
– The G protein is like a pull-back toy car. Pull it back to
“wind it up” (have it interact with the receptor), then
“let it go” (have it interact with the enzyme).
Back to G Protein-Coupled Receptors
• Deactivation:
– The enzyme hydrolyzes GTP and removes a phosphate.
– The G protein is released. The process can start again.
And I care…because?
• So why are G protein-coupled receptors
important?
– Your vision and smell senses use G proteincoupled receptors.
– Diseases like botulism, pertussis (whooping
cough), and cholera produce toxins that interfere
with GPCRs.
– Around 60% of medicine works by affecting
GPCRs, and a whole lot of drugs (including heroin)
work the same way.
G Protein-Coupled Receptor
Case in Point
• Cholera is caused by the
bacterium Vibrio cholerae.
• The bacterium releases a
toxin that prevents GTP
from being
dephosphorylated, leading
to a ton of salt secretion
from intestinal cells,
followed by water loss
through osmosis.
– This leads to fatal diarrhea if
not treated.
http://sameens.dia.uned.es/Trabajos10/Trab_Publicos/Trab_2/Navarro_De_La_Cruz_2/Imagenes/vibrio_cholerae%5B1%5D.jpg
2. Tyrosine-Kinase Receptors
• Tyrosine-kinase is an enzyme
stuck in the cell membrane.
• Its job is to dephosphorylate
ATP and move that
phosphate group to the
attached tyrosine.
• It has a binding site in the
ECM for signal molecules
and single α helix in the
membrane.
Tyrosine-Kinase Receptors
• Inactive
– The tyrosine-kinase receptor proteins are two separate
monomers, and relay proteins are not active.
• Take a guess where this is going…
Tyrosine-Kinase Receptors
• Activated
– A ligand activates the monomers and they make a dimer.
– Once joined, the kinase dephosphorylates ATP and adds that
phosphate group to its tyrosine (amino acid), which activates
relay proteins.
Tyrosine-Kinase vs. G Protein
• G proteins tend to elicit only one type of
response per G protein.
• A single tyrosine-kinase receptor can cause
multiple responses.
– Errant receptor tyrosine-kinases have been linked
to cancer.
3. Ion Channel
Receptors
• These are protein channels
that open only when
activated by a ligand.
• Nerve cells use these
frequently.
– Uh…that’s it here.
Receptors: Big Ideas
• Versatility: Different cell types can respond to
the same ligand in different ways:
Receptors: Big Ideas
• Scaffolding: Some proteins serve as intermediates
and hold relay proteins together.
Receptors: Big Ideas
• Amplification: A single
signal molecule can
lead to a massive
response.
– This is the point of a
phosphorylation
cascade.
Second Messengers
• Signal transduction pathways often activate second
messengers.
– These are molecules within cells that act as signals just
like the original extracellular signal.
• The three major classes of second messengers:
– Cyclic nucleotides
– DAG and IP3
– Calcium ions (Ca2+)
Second Messenger:
Cyclic Nucleotides
• The enzyme adenylyl cyclase is activated by a
G protein.
– Adenylyl cyclase uses ATP to make cAMP, or cyclic
AMP.
– AMP = adenosine monophosphate
• Similarly, guanylyl cyclase uses GTP to make
cGMP (cyclic GMP).
• These second messengers then serve to turn
on other responses within cells.
Second Messenger:
IP3 and DAG
• DAG is diacylglycerol which stays in the cell
membrane and activates other enzymes,
which often use…
• …IP3, which is inositol triphosphate.
– This helps release Ca2+ ions (which are themselves
considered a second messenger) from the ER.
• Calcium ions, by the way, are used widely
throughout the body.
– Including making your muscles contract.
Time to Practice
• Signal Transduction Pathways POGIL
The Endocrine System
• Those signaling methods we just saw operate on
relatively “local” distances.
• When operating on long distances, we’re talking
about hormones.
– In Greek, harmon means “to excite.”
• Key: Hormones reach every cell in the body but
only affect those with specific receptors.
– Everyone hears it, but only some can respond.
• Local signaling = whispering.
• Hormones = YELLING but in a different language.
“When I get nervous I release
hormones…”
• It turns out that the nervous system is very
much like the endocrine system.
• Both utilize signals between cells.
– When it’s a signal molecule released from nerve
to nerve, it’s called a neurotransmitter, but there’s
really nothing that different between them.
– They both use feedback and they also can
sometimes be released by the same structures.
The Endocrine System
• Endocrine glands secrete chemical signals within
the body.
– Hence the name “endocrine.”
• Exocrine glands secrete chemical signals onto the
outside of the body or into a cavity.
– Examples include salivary glands and sweat glands.
• Women’s menstrual cycles can be influenced by other
women’s sweat.
– Other examples include anal glands in dogs and cats
(and other animals).
• Don’t worry, no photo.
The Endocrine System
• Hormones tend to be either water-soluble
(polar) or lipid-soluble (non-polar).
– Polar molecules use the same mechanisms as
extracellular responses (GPCRs, receptor tyrosine
kinases).
– Non-polar molecules act like intracellular signals.
• They go all the way into the cell and bind with
receptors within the cytoplasm, remember?
Hormone Mechanisms
Another View
Important Components of the
Endocrine System
• Pineal Gland
– Produces melatonin, which regulates circadian (day/seasonal) rhythms.
• Pituitary Gland/Hypothalamus
– Makes growth hormone (GH), regulates menstrual cycle, and
pigmentation.
• Pancreas
• Ovaries/Testes (gonads)
– Male hormones = androgens (including testosterone)
– Female hormones = estrogens (including estradiol) and progestogens
(including progesterone)
• Thyroid/Parathyroid Gland
– Regulate energy usage and nervous system function.
• Gastrointestinal Tract
• Adrenal Glands
– Respond to stress, release epinephrine (adrenaline).
Aside: Clown Anemonefish
• You’ve seen Finding Nemo, right?
• What that movie didn’t tell you is that clownfish (clown
anemonefish, officially) have an interesting structure in
their social groups.
• There is only one female and one reproductive male.
– All others are smaller males whose sperm is inhibited by the
female. All clown anemonefish are born male.
• When the female dies, the reproductive male becomes
female with a rush of estradiol hormone.
– The next biggest (not necessarily oldest) male becomes the
reproductive male.
http://2.bp.blogspot.com/-0aMlLqUGGLI/TV9-haWanCI/AAAAAAAAAzk/goTrWowOCZE/s1600/2c64d3bfebwnfish.jpg.jpg
Aside: Clown Anemonefish
• What does this mean?
• It means that, assuming there were no other
individuals in Nemo’s group, after Nemo’s mom’s
death, Nemo’s dad will soon become Nemo’s mom.
• Nemo, meanwhile, will become reproductive and
mate with his fathermother, until heshe dies and
Nemo becomes female, perhaps mating with his
own offspring.
– Dory should have just stayed away…
http://2.bp.blogspot.com/-0aMlLqUGGLI/TV9-haWanCI/AAAAAAAAAzk/goTrWowOCZE/s1600/2c64d3bfebwnfish.jpg.jpg
The Endocrine System
Some Important Hormone Information
• The illegal anabolic steroids in sports are actually
analogs of androgens.
• Insulin (blood sugar reducer) and glucagon (blood sugar
increaser) are hormones.
• Dwarfism is caused by a lack of growth hormone from
the pituitary.
• Acromegaly is a sort of dwarfism opposite caused by
increased growth hormone.
• The thyroid gland makes thyroxine (an iodine-based
hormone) used in regulating basal metabolic rates.
• Epinephrine (adrenaline) and norepinephrine are made
by the adrenal glands that sit atop the kidneys (the
renal organs).
It’s Peanut Butter POGIL Time!
• Cell Communication POGIL
The Catch: Homeostasis
• All this signaling is great, but there’s one
major catch: organisms still need to maintain
homeostasis.
• They can achieve this through feedback loops.
• Positive feedback amplifies the original signal.
• Negative feedback inhibits the original signal.
– As you might guess, negative feedback is far more
useful to homeostasis.
Negative Feedback
Examples
• Predator-Prey Relationships
– Increase in prey leads to an
increase in predators…which
decreases prey.
• Body Temperature
– A rise in body temperature is
sensed by neurons which
signal the brain, which sends
signals to dilate the blood
vessels (vasodilation),
decreasing temperature.
• And making you red in the
face.
Negative Feedback
Another Example
• If the pH in the
duodenum (part of the
intestine) drops too low…
• …the cells in the intestine
release secretin, a
chemical signal, into the
blood.
• Secretin travels to the
pancreas, which releases
bicarbonate…
• …which raises the pH.
Positive Feedback
Examples
• Stampedes
– A few animals start to
stampede, causing more to run,
leading to a mass movement.
• Uterine contractions
– Oxytocin causes uterine
contractions, which moves the
fetus further down the birth
canal, which stimulates more
oxytocin release.
• Students packing up at the
end of class?
Awkward stock photo from old
PowerPoint…at what exactly are they
all looking?
Positive Feedback
Another Example
• If a break occurs in a blood
vessel…
• …platelets adhere to it and
release chemicals…
• …which attract more
platelets until the process
ends.
Positive Feedback
One last one…
• The ocean is a major carbon sink.
• Carbon dioxide dissolves best in cold water.
• As CO2 levels cause temperatures to rise, more
CO2 precipitates from the ocean.
• More CO2 coming out of the ocean raises
temperatures…
• …which releases more CO2.
Coupling Feedback Loops
• Remember that negative feedback loops are best
for homeostasis.
• To prevent any level or rate from getting too high,
you need a feedback loop.
• To prevent any level or rate from getting too low,
you need another feedback loop.
• Key: A coupled (or double) feedback loop is
needed to keep homeostasis.
– Let’s look at some examples. Know the key
components.
Calcium Homeostasis
Calcitonin
released
Blood
Ca2+
Blood Ca2+
lowered
high
Calcium
Homeostasis
Blood Ca2+
raised
Blood Ca2+ low
Parathyroid Hormone
(PTH) released
Glucose Homeostasis
Insulin
released
Blood glucose
high
Blood glucose
lowered
Glucose
Homeostasis
Blood glucose
raised
Blood glucose
low
Glucagon
released
Closure: Feedback Mechanisms POGIL
• It’s time to put our knowledge of feedback
mechanisms to the test using a POGIL.
• Feedback Mechanisms POGIL