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Transcript
Why Do Cells Communicate?
Cell Signaling (C.S.)
Regulation
• Cells need to control cellular processes
• In multicellular organism, cells signaling
pathways coordinate the activities within
individual cells that support the function of the
organism as a whole
Environmental Stimuli
• Cells need to be able to respond to signals
from their environment
• Single celled organisms use cell signaling
pathways to respond to their environment
•
•
•
Stages of Cell Signaling
Reception
Is a relatively “new” topic in Bio/AP Bio
Appears to answer many questions in
medicine
Especially since signal transmission within and
between cells mediated gene expression
(causes genes to turn on and off)
1. Reception- receiving the signal
2. Transduction- passing on the signal
3. Response- cellular changes because of the
signal
•
The target cell’s detection of a signal coming
from outside the cell
May Occur by:
• Direct connect
• Through signal molecules
Direct Connect
When molecules can flow directly from cell to
cell without crossing membranes
• Plants- plasmodesmata
• Animals- gap junctions
• Reception may also occur by cell surface
molecules that project from the surface and
“touch” another cell
Example
-Interaction between cells of the immune system
Signal Molecules
• The actual chemical signal that travels from cell
to cell
• Often water soluble b/c of polarity
• Usually too large to travel through membranes
• Behave as “ligands”: a smaller molecule that
binds to a large one
• Signal molecules can be local regulators that
target cells within the vicinity of the emitting cell
(neurotransmitters), or they can travel long
distances to target cells of another type
(hormones)
Receptor Molecules
• Usually made of protein: highly specific 3-D
shape to only bind with their specific signal
molecule (ligand)
• Change shape when bind to a signal molecule,
initiating transduction (Conformation change)
• Transmits information from the exterior to the
interior of a cell
Receptor Mechanisms
•
1.
2.
3.
4.
G-Protein linked
Tyrosine-Kinase
Ion Channels
Interacellular
G-Protein Linked
• Plasma membrane receptor
• Works with “G-Protein” an interacellular protein
w/ GDP & GTP
• GDP & GTP act as a switch
• GDP-inactive / GTP- active
• When active (GTP), the protein binds to another
protein (enzyme0 and alters its activation (turn it
on)
• Active site is only temporary
G-Protein Process: How epinephrine triggers the
conversion of glycogen into glucose
1.G-protein w/out ligand (no activation)
2.Ligand or epinephrine attaches (reception)
3.Activates subunit which moves w/ GTP across
the membrane
4.Attaches to enzyme (Adenylyl cyclase)
5.This converts ATP->cAMP
6.cAMP attaches to regulator side on a protein
kinase
7.Protein kinase releases the catalic side which
converts glycogen->glucose
8.Release ligand to stop
G-Protein Linked Receptors
• Very widespread and diverse in functions
Ex-vision, smell, blood vessels development
• Many diseases work by affecting g-protein linked
receptors
Ex-Whooping cough, botulism, cholera, some
cancers
• Up to 60% of all medicines exert their effectd
through g-protein linked receptors
Tyrosine-Kinase Receptors
• Extends through the cell membrane
• Intracellular part functions as a “kinase”, which
transfers Pi from ATP to tyrosine on a substance
protein
• Unlike G-proteins that activate only one
pathway, these often activate several different
pathways at once, helping regulate complicated
functions such as cell division
Tyrosine-Kinase Receptor Mechanism
1.Ligand binding- causes two receptor molecules
to aggregate (Ex. Growth hormone)
2.Activation of tyrosine-kinase parts in cytoplasm
3.Phosphorylation of tyrosines by ATP (sets off
several pathways)
Intracellular Proteins
• Become activated and case the cellular response
Ion Channel Receptors
• Protein pores in the membrane that open or
close in response to chemical signals
• Allow or block the flow of ions such as Na+ or
Ca2+
• Activated by a ligand on the extracellular side
• Causes a change in ion concentration inside the
cell
Ex-Nervous system signals
Intracellular Signals
• Proteins located in the cytoplasm or nucleus that
receive a signal that CAN pass through the cell
membrane (small/nonpolar)
Ex-Steroids (hormones) No-nitric oxide
• Activated protein turns on genes in nucleus
• Most signals never enter a cell, the signal is
received at the membrane and passed on
Exception-intracellular receptors
Signal-Transduction Pathways
• The further amplification and movement of a
signal in the cytoplasm to cause a cellular
response
• Often has multiple steps using relay proteins
such as protein kinases
Protein Phosphorylation
• The addition of Pi to a protein which activates
the protein
Protein Kinase
Secondary Messengers
cAMP
• General name for any enzyme that transfers Pi
from ATP to a protein
Amplification
• Often works in a cascade w/ each being able to
activate several molecules
• Result-from one signal, many molecules can be
activated
• Signaling pathways w/ numerous
steps(cascades):
-Often involve the use of second messengers to
facilitate the cascade
-Amplify a signal response in a cell
-Provide different points at which the response
can be regulated
• Small water soluble, non-protein molecules or
ions that pass on a signal (Live in the cytoplasmwater)
• Spread rapidly by diffusion
• Activate relay proteins
Examples
-cAMP
-Ca2+
-Inositol Trisphosphate (IP3)
• Activates a number of protein kinase
Calcium Ions
• More widely used the cAMP
• Used as a secondary messenger in both Gprotein pathways and tyrosine-kinase receptor
pathways
Inositol Trisphosphate (IP3)
• Secondary messenger attached to phospholipid
of the cell membrane
• Sent to Ca channels on the ER
• Allows a flood of Ca2+ into the cytoplasm from
the ER, activating a cell response
Cellular Response
• Cytoplasmic regulation
• Regulation of gene expression
-Transcription regulation in the nucleus (DNA>RNA)
Cytoplasmic Regulation
• Rearrangement of the cytoskeleton
• Opening or closing of an ion channels
• Alteration of cell metabolism
Transcription Regulation
• Activating protein synthesis for new enzymes
• Transcription control factors are often
activated by a protein kinase
If liver and heart cells both are exposed to ligands,
why does one respond and the other not?
• Different cells have different collections of
receptors
Apoptosis (Programmed cell death)
• An elaborate ex of cell signaling that causes
controlled cell suicide
• During this process the cell is dismantled and
digested through many CS pathways to protect
neighboring cells from damage
• Triggered by signals that activate a cascade of
suicide proteins in cells
• In vertebrates, this is a normal part of
development for our nervous immune systems