CHAPTER 9
LECTURE
SLIDES
To run the animations you must be in
Slideshow View. Use the buttons on the
animation to play, pause, and turn audio/text
on or off. Please note: once you have used
any of the animation functions (such as Play or
Pause), you must first click in the white
background before you advance the next slide.
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Cell Communication
Chapter 9
Overview
• Communication between cells requires
• Ligand – signaling molecule
• Receptor protein – molecule to which the
receptor binds
• Interaction of these two components
initiates the process of signal transduction,
which converts the information in the
signal into a cellular response
3
4
• There are four basic mechanisms for
cellular communication
1.Direct contact
2.Paracrine signaling
3.Endocrine signaling
4.Synaptic signaling
• Some cells send signals to themselves
(autocrine signaling)
5
• Direct contact
• Molecules on the
surface of one cell are
recognized by
receptors on the
adjacent cell
• Important in early
development
• Gap junctions
6
• Paracrine signaling
• Signal released from
a cell has an effect on
neighboring cells
• Important in early
development
• Coordinates clusters
of neighboring cells
• Signaling between
immune cells
7
• Endocrine signaling
• Hormones released
from a cell travel
through circulatory
system to affect other
cells throughout the
body
• Both animals and
plants use this
mechanism extensively
8
• Synaptic signaling
• Animals
• Nerve cells release
the signal
(neurotransmitter)
which binds to
receptors on nearby
cells
• Association of neuron
and target cell is a
chemical synapse
9
Signal transduction
• Events within the cell that occur in
response to a signal
• When a ligand binds to a receptor protein,
the cell has a response
• Different cell types can respond differently
to the same signal
– Epinephrine example
10
Phosphorylation
• Addition of phosphate group
• A cell’s response to a signal often involves
activating or inactivating proteins
• Phosphorylation is a common way to
change the activity of a protein
• Protein kinase – an enzyme that adds a
phosphate to a protein
• Phosphatase – an enzyme that removes a
phosphate from a protein
11
12
Receptor Types
• Receptors can be defined by their location
1.Intracellular receptor – located within the
cell
2.Cell surface receptor or membrane
receptor – located on the plasma
membrane to bind a ligand outside the cell
– Transmembrane protein in contact with both
the cytoplasm and the extracellular
environment
13
3 subclasses of membrane
receptors
1. Chemically gated ion channels – channellinked receptors that open to let a specific
ion pass in response to a ligand
2. Enzymatic receptors – receptor is an
enzyme that is activated by the ligand
– Almost all are protein kinases
3. G protein-coupled receptor – a G-protein
(bound to GTP) assists in transmitting the
signal from receptor to enzyme (effector)
14
15
Intracellular Receptors
• Steroid hormones
– Common nonpolar, lipid-soluble structure
– Can cross the plasma membrane to a steroid
receptor
– Binding of the hormone to the receptor
causes the complex to shift from the
cytoplasm to the nucleus
– Act as regulators of gene expression
16
17
• A steroid receptor has 3 functional
domains
1.Hormone-binding domain
2.DNA-binding domain
3.Domain that interacts with coactivators to
affect level of gene transcription
• In its inactive state, the receptor typically
cannot bind to DNA because an inhibitor
protein occupies the DNA binding site
• Binding of ligand changes conformation
18
Please note that due to differing
operating systems, some animations
will not appear until the presentation is
viewed in Presentation Mode (Slide
Show view). You may see blank slides
in the “Normal” or “Slide Sorter” views.
All animations will appear after viewing
in Presentation Mode and playing each
animation. Most animations will require
the latest version of the Flash Player,
which is available at
http://get.adobe.com/flashplayer.
19
Coactivators
• Target cell’s response to a lipid-soluble cell
signal can vary enormously, depending on the
nature of the cell
• Even the same type of cell may have different
responses
• Depends on coactivators present
• Estrogen has different effects in uterine tissue
than mammary tissue
– Not presence or absence of receptor
– Presence or absence of coactivator
20
Receptor Kinases
• Protein kinases phosphorylate proteins to
alter protein function
• Receptor tyrosine kinases (RTK)
– Influence cell cycle, cell migration, cell
metabolism, and cell proliferation
• Alteration to function can lead to cancer
– Membrane receptor
– Plants possess receptors with a similar overall
structure and function
21
• RTKs have
– A single transmembrane domain
• Anchors them in membrane
– Extracellular ligand-binding domain
– Intracellular kinase domain
• Catalytic site of receptor acts as protein kinase
• When a ligand binds, dimerization and
autophosphorylation occur
• Cellular response follows – depends on
cellular response proteins
22
23
• Insulin receptor
• Activated receptor
has phosphorylated
sites that allow
docking
• Insulin is a hormone
that helps to maintain
a constant blood
glucose level
• Lowers blood glucose
24
Kinase cascade
• Mitogen-activated protein (MAP) kinases
– Important class of cytoplasmic kinases
– Mitogens stimulate cell division
– Activated by a signaling module called a
phosphorylation cascade or kinase cascade
– Series of protein kinases that phosphorylate
each other in succession
– Amplifies the signal because a few signal
molecules can elicit a large cell response
25
26
27
G-Protein Coupled Receptors
G-protein – protein bound to GTP
G-protein-coupled receptor (GPCRs) –
receptors bound to G proteins
-G-protein is a switch turned on by the
receptor
-G-protein then activates an effector protein
(usually an enzyme)
28
Scaffold proteins
• Thought to organize the
components of a kinase
cascade into a single
protein complex
• Binds to each individual
kinase such that they are
spatially organized for
optimal function
• Benefit in efficiancy
• Disadvantage in reducing
amplification effect
29
Ras proteins
• Small GTP-binding protein (G protein)
• Link between the RTK and the MAP
kinase cascade
• Ras protein is mutated in many human
tumors, indicative of its central role in
linking growth factor receptors to their
cellular response
• Ras can regulate itself – stimulation by
growth factors is short-lived
30
31
G-Protein Coupled Receptors
• Single largest category of receptor type in
animal cells is GPCRs
• Receptors act by coupling with a G protein
• G protein provides link between receptor
that receives signal and effector protein
that produces cellular response
• All G proteins are active when bound to
GTP and inactive when bound to GDP
• Effector proteins are usually enzymes
32
33
• Often, the effector proteins activated by G
proteins produce a second messenger
• 2 common effectors
1. Adenylyl cyclase
– Produces cAMP
– cAMP binds to and activates the enzyme protein
kinase A (PKA)
– PKA adds phosphates to specific proteins
2. Phospholipase C
– PIP2 is acted on by effector protein phospholipase C
– Produces IP3 plus DAG
– Both act as second messengers
34
35
36
• Calcium
• Ca2+ serves widely as
second messenger
• Intracellular levels
normally low
• Extracellular levels quite
high
• Endoplasmic reticulum
has receptor proteins that
act as ion channels to
release Ca2+
• Most common receptor
binds IP3
37
Cell-to-Cell Interactions
Cells can identify each other by cell surface
markers
-Glycolipids are commonly used as tissuespecific markers
-Major histocompatibility complex (MHC)
proteins are used by cells to distinguish
“self” from “nonself”
38
• Different receptors can produce the same
second messengers
• Hormones glucagon and epinephrine can
both stimulate liver cells to mobilize
glucose
– Different signals, same effect
– Both act by same signal transduction pathway
39
40
• Single signaling molecule can have
different effects in different cells
• Existence of multiple forms of the same
receptor (subtypes or isoforms)
• Receptor for epinephrine has 9 isoforms
– Encoded by different genes
– Sequences are similar but differ in their
cytoplasmic domains
• Different isoforms activate different G
proteins leading to different signal
transduction pathways
41