I think she meantstaff.katyisd.org/sites/thsbiologyapgt/Documents...1 Reception 2 Transduction Response2 Activation of cellular response 3 Reception: signaling molecule binds to receptor

I think she meant

a different kind of

cellular communication…

Chapter 11

Cellular Communication

Don’t you get it? It’s

not what I said, it’s

what I meant to say!…

External signals are converted to responses within the cell

© 2011 Pearson Education, Inc.

Exchange

of mating

factors

Receptor factor

Yeast cell, mating type a

Yeast cell, mating type

Mating

New a/ cell

1

2

3

a

a

a/

Yeast has two mating types,

a and Cells locate each other via

secreted factors (pheromones)

Signal Transduction Pathway

series of steps that convert a

signal on a cell’s surface into

a specific cellular response.

a factor

• Pathway similarities

suggest ancestral signaling

molecules evolved in

prokaryotes and later

modified in eukaryotes.

• Quorum Sensing –

Signal molecule

concentration allows bacteria

to sense population density.


Figure 11.3

Individual

rod-shaped

cells

Spore-forming

structure

(fruiting body)

Aggregation

in progress

Fruiting bodies

1

2

3

Common trait,

common ancestry…

Long-Distance and Local Signaling • Cells in a multicellular organism

communicate by chemical messengers.

• Animal and plant cells use

cell junctions directly

connect cytoplasm of adjacent

cells

And

• Local signaling communication by direct

contact, or by cell-cell recognition


Plasma membranes

Gap junctions

between animal cells

Plasmodesmata

between plant cells

(a) Cell junctions

(b) Cell-cell recognition

(b) Cell-cell recognition

• Long-Distance

Signaling plants and animals use

chemicals called hormones

• The ability of a cell to

respond to a signal depends

on presence of the receptor

specific to that signal


Long-distance signaling

Endocrine cell Blood

vessel

Hormone travels

in bloodstream.

Target cell

specifically

binds

hormone.

(c) Endocrine (hormonal) signaling

• Local Signaling messenger molecules that travel only short distances


Target cell

Secreting

cell Secretory

vesicle

Local regulator

diffuses through

extracellular fluid.

(a) Paracrine signaling (b) Synaptic signaling

Electrical signal

along nerve cell

triggers release of

neurotransmitter.

Neurotransmitter

diffuses across

synapse.

Target cell

is stimulated.

Three Stages of Cell Signaling:

• Earl W. Sutherland discovered how the

hormone epinephrine acts on cells

• Sutherland suggested that cells receiving

signals went through three processes

– Reception

– Transduction

– Response


Figure 11.6-1

Plasma membrane

EXTRACELLULAR

FLUID CYTOPLASM

Reception

Receptor

Signaling

molecule

1

Plasma membrane

EXTRACELLULAR

FLUID CYTOPLASM

Reception Transduction

Receptor

Signaling

molecule

Relay molecules in a signal transduction

pathway

2 1

Plasma membrane

EXTRACELLULAR

FLUID CYTOPLASM

Reception Transduction Response

Receptor

Signaling

molecule

Activation

of cellular

response Relay molecules in a signal transduction

pathway

3 2 1

Reception: signaling molecule binds to receptor protein, causing

conformation change.

The binding between a signal molecule (ligand) and receptor is highly

specific

A shape change in a receptor is often the initial transduction of the signal

Most signal receptors are plasma membrane proteins

Types of Receptors in the Plasma Membrane

• Water-soluble signal molecules bind to specific sites on receptor proteins that span the plasma membrane

• There are three main types of membrane

receptors

–G protein-coupled receptors

–Receptor tyrosine kinases

–Ion channel receptors



• G protein-coupled receptors (GPCRs) • Largest family of cell-surface receptors.

• Works with the help of a G protein (Guanine nucleotide-

binding proteins) - acts as an on/off switch.

“off” when bound to GDP (Guanine diphosphate)

“on” when bound to GTP (Guanine triphosphate)

You know what turns me on! …and off!

//upload.wikimedia.org/wikipedia/commons/8/8c/Guanosindiphosphat_protoniert.svg

//upload.wikimedia.org/wikipedia/commons/2/2c/Guanosintriphosphat_protoniert.svg

Figure 11.7b

G protein-coupled

receptor

2 1

3 4

Plasma membrane

G protein (inactive)

CYTOPLASM Enzyme

Activated receptor

Signaling molecule

Inactive enzyme

Activated enzyme

Cellular response

GDP GTP

GDP GTP

GTP

P i

GDP

GDP

http://www.youtube.com/watch?

v=4dUJ5GNpfrA&feature=endsc

reen&NR=1

http://www.youtube.com/watch?v=4dUJ5GNpfrA&feature=endscreen&NR=1

• Receptor tyrosine kinases (RTKs) receptors that attach phosphates to tyrosines

• A receptor tyrosine kinase can trigger

multiple signal transduction pathways at once

• Abnormal functioning of RTKs is associated

with many types of cancers


Figure 11.7c

Signaling

molecule (ligand)

2 1

3 4

Ligand-binding site

helix in the

membrane

Tyrosines

CYTOPLASM Receptor tyrosine kinase Proteins (inactive monomers)

Signaling

molecule

Dimer

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

P

P

P

P

P

P

P

P

P

P

P

P

Activated tyrosine

kinase regions

(unphosphorylated

dimer)

Fully activated

receptor tyrosine

kinase

(phosphorylated

dimer)

Activated relay

proteins

Cellular

response 1

Cellular

response 2

Inactive

relay proteins

6 ATP 6 ADP

Figure 11.7d

Signaling molecule (ligand)

2 1 3

Gate closed Ions

Ligand-gated ion channel receptor

Plasma membrane

Gate open

Cellular response

Gate closed

• Ligand-gated ion channel receptors acts as gates when the receptors change shape.

• When a signal molecule binds as a ligand to the receptor,

the gate allows specific ions, such as Na+ or Ca2+, through

a channel in the receptor

Intracellular Receptors • Intracellular receptor proteins are found in the

cytosol or nucleus of target cells

• Small or hydrophobic chemical messengers can

readily cross the membrane and activate receptors

• Examples of hydrophobic messengers are the

steroid and thyroid hormones of animals

• An activated hormone-receptor complex can act

as a transcription factor, turning on specific

genes

Figure 11.9-1

Hormone (testosterone)

Receptor protein

Plasma membrane

DNA

NUCLEUS

CYTOPLASM

EXTRACELLULAR FLUID


Receptor protein

Plasma membrane

Hormone- receptor complex

DNA

NUCLEUS

CYTOPLASM

EXTRACELLULAR FLUID


Receptor protein

Plasma membrane


DNA

NUCLEUS

CYTOPLASM

EXTRACELLULAR FLUID


Receptor protein

Plasma membrane


DNA

mRNA

NUCLEUS

CYTOPLASM

EXTRACELLULAR FLUID


Receptor protein

Plasma membrane

EXTRACELLULAR FLUID


DNA

mRNA

NUCLEUS

CYTOPLASM

New protein

I like this Testosterone stuff!

Transduction:

Cascades of molecular interactions relay signals

from receptors to target molecules in the cell

• Signal transduction usually involves multiple steps

• Can amplify a signal: A few molecules can

produce a large cellular response

• provide more opportunities for coordination and

regulation of the cellular response


Signal Transduction Pathways

• The molecules that relay a signal from

receptor to response are mostly proteins.

• Like falling dominoes, the receptor

activates another protein, which

activates another, and so on, until the

protein producing the response is

activated.

• At each step, the signal is transduced into a

different form, usually a conformational

change in a protein. © 2011 Pearson Education, Inc.

Protein Phosphorylation and

Dephosphorylation

• In many pathways, the signal is transmitted by

a cascade of protein phosphorylations.

• Protein kinases transfer phosphates from

ATP to protein, a process called

phosphorylation.


• Protein phosphatases remove the

phosphates from proteins, a process called

dephosphorylation.

• This phosphorylation and

dephosphorylation system acts as a

molecular switch, turning activities on and

off or up or down, as required.


Activated relay molecule

Inactive protein kinase

1 Active

protein kinase

1

Active protein kinase

2

Active protein kinase

3


2


3

Inactive protein

Active protein

ATP

ADP

ATP ADP

ATP

ADP

PP

PP

PP

P

P

P i

P i

P i

P

Figure 11.10a Signaling molecule

Cellular response

Small Molecules and Ions as Second Messengers

• “First messenger” - extracellular signal

molecule (ligand) binds to the receptor.

• Second messengers - small, nonprotein,

water-soluble molecules or ions that spread

throughout a cell by diffusion.

ex. - Cyclic AMP and calcium ions

• Second messengers participate in pathways

initiated by GPCRs and RTKs


Cyclic AMP • Cyclic AMP (cAMP) - widely used second messenger.

• Adenylyl cyclase converts ATP to cAMP in response to

an extracellular signal.


Adenylyl cyclase Phosphodiesterase

Pyrophosphate

AMP

H2O

ATP

P i P

cAMP

cAMP usually activates protein kinase A, which

phosphorylates various other proteins.

Further regulation of cell metabolism is provided by G-protein

systems that inhibit adenylyl cyclase (which shuts down cAMP

production).

Figure 11.12

G protein

First messenger (signaling molecule such as epinephrine)

G protein-coupled receptor

Adenylyl cyclase

Second messenger

Cellular responses

Protein kinase A

GTP

ATP

cAMP

Calcium Ions and Inositol Triphosphate (IP3)

• Calcium ions (Ca2+) act

as a second messenger in many

pathways

• important second messenger as

cells can regulate its concentration

• Pathways leading to the release of

calcium involve

• inositol triphosphate (IP3) and

diacylglycerol (DAG) as additional

second messengers


Mitochondrion

EXTRACELLULAR FLUID

Plasma membrane

Ca2 pump

Nucleus

CYTOSOL

Ca2 pump

Ca2 pump

Endoplasmic reticulum (ER)

ATP

ATP

Low [Ca2 ] High [Ca2 ] Key

Figure 11.14-3

G protein

EXTRA- CELLULAR FLUID

Signaling molecule (first messenger)

G protein-coupled receptor

Phospholipase C

DAG

PIP2

IP3

(second messenger)

IP3-gated calcium channel

Endoplasmic reticulum (ER)

CYTOSOL

Various proteins activated

Cellular responses

Ca2 (second messenger)

Ca2

GTP

Nuclear and Cytoplasmic

Responses

• Signal transduction pathway leads to regulation of cellular activities

• Many signaling pathways regulate the synthesis of enzymes or other proteins by turning genes on or off in the nucleus

• The final activated molecule in the signaling pathway may function as a transcription factor.


Growth factor

Receptor

Reception

Transduction

CYTOPLASM

Response

Inactive transcription factor

Active transcription factor

DNA

NUCLEUS mRNA

Gene

Phosphorylation cascade

P

Fine-Tuning of the Response

– Amplification of the signal

- Enzyme Cascades

– Specificity of the response

- Different cells, different proteins, different responses

– Overall efficiency of response, enhanced by

scaffolding proteins - Grouping together proteins involved in the same pathway

– Termination of the signal If ligand concentration falls, fewer receptors will be bound.

Unbound receptors revert to an inactive state.

Apoptosis is programmed or

controlled cell suicide

• Components of the cell are chopped up and packaged

into vesicles that are digested by scavenger cells

• Apoptosis prevents enzymes from leaking out of a

dying cell and damaging neighboring cells


• Apoptosis can be triggered by

– An extracellular death-signaling ligand

– DNA damage in the nucleus

– Protein misfolding in the endoplasmic reticulum

• Apoptosis evolved early in animal evolution

and is essential for the development and

maintenance of all animals

• Apoptosis may be involved in some diseases

(for example, Parkinson’s and Alzheimer’s);

interference with apoptosis (defective p53

gene) may contribute to some cancers.


Interdigital tissue

Cells undergoing apoptosis

Space between digits 1 mm

LECTURE PRESENTATIONS

For CAMPBELL BIOLOGY, NINTH EDITION Jane B. Reece, Lisa A. Urry, Michael L. Cain, Steven A. Wasserman, Peter V. Minorsky, Robert B. Jackson


Lectures by

Erin Barley

Kathleen Fitzpatrick

Ch. 45 Hormones and the

Endocrine System

Overview: The Body’s Long-Distance

Regulators

• Animal hormones are chemical signals that are

secreted into the circulatory system and

communicate regulatory messages within the

body

• Hormones reach all parts of the body, but only

target cells have receptors for that hormone



• Two systems coordinate communication throughout the body:

• The endocrine system secretes hormones that coordinate slower but longer-acting responses including reproduction, development, energy metabolism, growth, and behavior

• The nervous system conveys high-speed electrical signals along neurons; these signals regulate other cells

Hormones bind to target receptors,

triggering specific response pathways


Intercellular Communication

• Signals transmitted between animal cells are

classified by two criteria:

– The type of secreting cell

– The route taken by the signal in reaching its target

(a) Endocrine signaling

(b) Paracrine signaling

(c) Autocrine signaling

(d) Synaptic signaling

(e) Neuroendocrine signaling

Figure 45.2a

(a) Endocrine signaling

Blood vessel Response

Response

Response

(b) Paracrine signaling

(c) Autocrine signaling

Hormones secreted by

endocrine cells reach

their targets via the

bloodstream

Local regulators

molecules act over

short distances,

reaching target cells

solely by diffusion

In paracrine signaling,

the target cells lie near

the secreting cells

In autocrine signaling,

the target cell is also

the secreting cell

Figure 45.2b

Synapse

Response

Response

Neuron

Synaptic signaling

Neurosecretory cell

Blood vessel

(e) Neuroendocrine signaling

• Synaptic Signaling - neurons form specialized junctions with

target cells, called synapses

• At synapses, neurons secrete

molecules called neurotransmitters

that diffuse short distances

and bind to receptors on

target cells

• Neuroendocrine Signaling

-specialized neurosecretory

cells secrete molecules

called neurohormones that

travel to target cells via the

bloodstream

Signaling by Pheromones


Deer

Wallow

• Molecular communication among members of the same

animal species using pheromones, chemicals that are

released into the environment

• Pheromones serve many functions:

marking trails leading to food,

defining territories

warning of predators

attracting potential mates

Endocrine Tissues and Organs

• Endocrine glands

• Endocrine cells grouped together in ductless

organs that secrete hormones directly into

surrounding fluid

• Exocrine glands

• Glands with ducts that secrete substances onto

body surfaces or into cavities


Figure 45.4

Hypothalamus

Pineal gland

Pituitary gland

Thyroid gland

Parathyroid glands (behind thyroid)

Adrenal glands (atop kidneys)

Pancreas

Ovaries (female)

Testes (male)

Organs containing endocrine cells:

Thymus

Heart

Liver

Stomach

Kidneys

Small intestine

Endocrine Tissues

and Organs

Chemical Classes of Hormones

• Three major classes of molecules function as

hormones in vertebrates

Polypeptides (proteins and peptides)

Amines derived from amino acids

Steroid hormones


Figure 45.6-2

Lipid- soluble hormone

SECRETORY CELL

Water- soluble hormone

VIA BLOOD

Signal receptor

TARGET CELL

OR

Cytoplasmic response Gene

regulation

(a) (b)

Cytoplasmic response Gene

regulation

Signal receptor

Transport protein

NUCLEUS

Water-soluble

hormones

(hydrophilic)

polypeptides

and

amines

Binds to cell

surface receptor.

Lipid-soluble

hormones

(hydrophobic)

steroid

hormones

pass easily

through cell

membranes Initiates a signal

transduction

pathway leading

to responses in

the cytoplasm,

enzyme

activation, or a

change in gene

expression

Pathway for Lipid-Soluble Hormones

• The response to a lipid-soluble hormone is

usually a change in gene expression

• Steroids, thyroid hormones, and the hormonal

form of vitamin D bind to protein receptors in the

cytoplasm or nucleus

• Protein-receptor complexes then act as

transcription factors in the nucleus


• A negative feedback loop inhibits a response by

reducing the initial stimulus, thus preventing

excessive pathway activity

• Positive feedback reinforces a stimulus to

produce an even greater response

• For example, in mammals oxytocin causes the

release of milk, causing greater suckling by

offspring, which stimulates the release of more

oxytocin


Feedback Regulation

Pathway Example

Stimulus

Low pH in duodenum

Endocrine cell

S cells of duodenum secrete the hormone secretin ( ).

Hormone

Blood vessel

Target cells of Pancreas

Response Bicarbonate release

Neg

ati

ve f

eed

back

Figure 45.11

• For example, the

release of acidic

contents of the

stomach into the

duodenum stimulates

endocrine cells there

to secrete secretin.

• This causes target

cells in the pancreas,

a gland behind the

stomach, to raise the

pH in the duodenum

by producing

bicarbonate (a base).

Pathway

Example

Stimulus Suckling

Sensory neuron

Po

sit

ive f

eed

back

Hypothalamus/ posterior pituitary

Neurosecretory cell

Neurohormone

Blood vessel

Target cells

Response

Posterior pituitary secretes the neurohormone oxytocin ( ).

Smooth muscle in breasts

Milk release

Figure 45.12

• In a simple

neuroendocrine

pathway, the

stimulus is received

by a sensory

neuron, which

stimulates a

neurosecretory cell

• The neurosecretory

cell secretes a

neurohormone,

which enters the

bloodstream and

travels to target cells

Insulin and Glucagon: Control of Blood Glucose

• Insulin (decreases blood glucose) and glucagon

(increases blood glucose) are antagonistic

hormones that help maintain glucose homeostasis

• The pancreas has clusters of endocrine cells called

pancreatic islets with alpha cells that produce

glucagon and beta cells that produce insulin


Figure 45.13a-1

Insulin

Beta cells of

pancreas

release insulin

into the blood.

Homeostasis:

Blood glucose level

(70–110 mg/100 mL)

STIMULUS:

Blood glucose level rises

(for instance, after eating a

carbohydrate-rich meal).

Figure 45.13a-2

Body cells

take up more

glucose.

Insulin

Beta cells of

pancreas

release insulin

into the blood.

Liver takes

up glucose

and stores it

as glycogen. Blood glucose

level declines.

Homeostasis:

Blood glucose level

(70–110 mg/100 mL)

STIMULUS:

Blood glucose level rises

(for instance, after eating a

carbohydrate-rich meal).

Figure 45.13b-1

Homeostasis:

Blood glucose level

(70–110 mg/100 mL)

Glucagon

STIMULUS:

Blood glucose level

falls (for instance, after

skipping a meal).

Alpha cells of pancreas

release glucagon into

the blood.

Figure 45.13b-2

Blood glucose

level rises.

Homeostasis:

Blood glucose level

(70–110 mg/100 mL)

Glucagon signals

Liver to break

down glycogen

and releases

glucose into

the blood.

Alpha cells of pancreas

release glucagon into

the blood. Glucagon

STIMULUS:

Blood glucose level

falls (for instance, after

skipping a meal).

Epinephrine

also, and really

fast…Why?

Body cells take up more glucose.

Insulin

Beta cells of pancreas release insulin into the blood.

Liver takes up glucose and stores it as glycogen.

Blood glucose level declines.

Blood glucose level rises.

Homeostasis: Blood glucose level

(70–110 mg/m100mL)

STIMULUS: Blood glucose level rises

(for instance, after eating a carbohydrate-rich meal).

Liver breaks down glycogen and releases glucose into the blood.

Alpha cells of pancreas release glucagon into the blood.

Glucagon

STIMULUS: Blood glucose level

falls (for instance, after skipping a meal).

Figure 45.13

Target Tissues for Insulin and Glucagon • Insulin reduces blood glucose levels by

– Promoting the cellular uptake of glucose

– Slowing glycogen breakdown in the liver

– Promotes fat storage, not breakdown

– Note: as long as your sugar intake is greater than

sugar requirements, you will always store the excess

as fat.


• Glucagon increases blood glucose levels by

– Stimulating conversion of glycogen to glucose in the liver

– Stimulating breakdown of fat and protein into glucose

Diabetes Mellitus

• Diabetes mellitus is perhaps the best-known endocrine

disorder

• Caused by a deficiency of insulin or a (insuling resistance)

in target tissues

• It is marked by elevated blood glucose levels


• Type 1 diabetes mellitus (insulin-dependent) is an

autoimmune disorder in which the immune system destroys

pancreatic beta cells

• Type 2 diabetes mellitus (non-insulin-dependent) involves

insulin deficiency or reduced response of target cells due to

change in insulin receptors

Thyroid Regulation: A Hormone Cascade

Pathway

• A hormone can stimulate the release of a series

of other hormones, the last of which activates a

nonendocrine target cell; this is called a hormone

cascade pathway

• The release of thyroid hormone results from a

hormone cascade pathway involving the

hypothalamus, anterior pituitary, and thyroid

gland

• Hormone cascade pathways typically involve

negative feedback


Disorders of Thyroid Function and

Regulation

• Hypothyroidism, too little thyroid function, can

produce symptoms such as

– Weight gain, lethargy, cold intolerance

• Hyperthyroidism, excessive production of

thyroid hormone, can lead to

– High temperature, sweating, weight loss,

irritability, and high blood pressure

• Malnutrition can alter thyroid function
