Transcript Cell Communication

Cell Communication
Chapter 11
p. 201-217
Evolution of Cell Signaling
• There is great similarity in
cell-signaling mechanisms of
yeasts & mammals
▫ Suggests the processes evolved
very long ago
• Signal Transduction
Pathway: process by which a
signal on cell’s surface is
converted into specific
cellular response
Local & Long-Distance Signaling
• Some cells communicate thru direct contact w/ one
another (i.e. plasmosdesmata)
• Local Regulators: message travels only short distance
▫ Paracrine Signaling: local regulator secretes message
into extracellular fluid
many neighboring cells
▫ Synaptic Signaling: neurotransmitters released into
synapse (space between 2 cells)
one target cell
• Long-Distance Signaling: uses hormones, released
into vessels, to carry signal throughout body to target
▫ Animals: endocrine signaling
▫ Plants: growth regulators
3 Stages of Cell Signaling: a preview
• 1) Reception: how target cell detects signal on
membrane surface or inside cell
• 2) Transduction: bound signal causes changes
that bring about a cellular response
▫ “Signal Transduction Pathway”
• 3) Response: can be almost anything
▫ i.e. catalysts, gene activation, etc
Reception: an overview
• Signals will only be “heard” by cells w/ specific
receptor proteins
▫ Signal molecule is complimentary in shape to
receptor
▫ Ligand: any molecule that specifically binds to
another (larger) molecule
 Usually causes receptor protein to change shape
Intracellular Receptors
• Located in cytoplasm or nucleus,
instead of plasma membrane
• Signal must pass through
cytoplasm of receptor cell (must
be small, hydrophobic)
▫ Testosterone: binds to receptor
protein in cytoplasm, both enter
nucleus & “turn on” genes for
male sex characteristics
Plasma Membrane Receptors
• H2O-soluble signals bind to receptors embedded
in plasma membrane
▫ Receptor then transmits info inside cell by
changing shape or aggregating (combining w/ 1+
other receptor proteins)
• 3 Types:
▫ G-protein-linked receptors
▫ Receptor tyrosine kinases
▫ Ion channel receptors
G-Protein-Linked Receptors
• Utilizes G protein (guanosine) to carry signal
from receptor enzyme further down in
membrane
▫ Activated enzyme triggers a cell response
• Consists of single polypeptide w/ 7 α helices
• Play role in: embryonic devlpmnt, vision,
cholera, botulism
▫ 60% modern medicines influence G-protein
pathways
Receptor Tyrosine Kinases
• Trigger more than 1 signal transduction pathway
at once
▫ Each may activate 10+ pathways & responses
▫ Help regulate & coordinate cell growth &
reproduction
• Kinase: an enzyme that catalyzes the transfer of
phosphate groups (from ATP tyrosine)
• Some abnormal RTK’s can function w/out a
signal, leading to cancer
Ion Channel Receptors
• Ligand-Gated Ion Channel: contains a
“gated” region that allows or blocks ions from
entering cell (Na+, Ca2+)
▫ When signal (ligand) binds, gate opens & ions
enter
▫ When ligand absent, gate is closed
▫ Play role in nervous system (neurotransmitters act
as ligands)
• Voltage-Gated Ion Channels: controlled by
electrical signals instead of ligands
Transduction: an overview
• Usually a multi-step process to bring signal from
receptor (on membrane) to target molecule
(inside cell)
▫ Signal may become amplified by activating
multiple molecules
 1 signal
large response; helps coordinate &
regulate processes
▫ Signal itself is not relayed, but information is
(conformational changes in proteins)
Protein Phosphorylation &
Dephosphorylation
• Protein Kinase “on”: enzyme that transfers a
phosphate group from ATP
a protein
▫ Usually serine or threonine (amino acids)
▫ Every time a phosphate is added to the next protein, causes
a conformational change (“activates” the protein)
▫ Regulates proteins involved in cell reproduction (mitosis &
meiosis)
▫ Abnormal protein kinases may cause abnormal cell growth
cancer
• Protein Phosphatases “off”: enzyme that removes a
phosphate from proteins (“dephosphorylation”)
▫ Deactivates protein & turns off signal transduction pathway
▫ Makes protein kinases available to do more work
Second Messengers
• Second Messenger: small, non-protein, H2O
soluble molecules or ions involved in signal
transduction pathways
▫ Readily spread through cell by diffusion
▫ Used with G-protein-linked receptors & RTK’s
▫ 2 Types:
 Cyclic AMP (cAMP)
 Ca2+ Ions & IP3
Cyclic AMP
• Involved in breakdown of glycogen glucose in
liver cells when epinephrine (signal) binds to Gprotein-linked receptor
▫ Adenylyl Cyclase: converts ATP cAMP when
signal binds
▫ Many cAMP made (signal is amplified) & signal is
broadcasted throughout cytoplasm
▫ cAMP activates protein kinase A, which
phosphorylates other proteins
 In cholera, bacteria modifies G protein so stays active &
keeps stimulating production of cAMP
 In Viagra, cGMP (cousin of cAMP) is inhibited, resulting
in dilation of blood vessels
Ca2+ Ions & IP3
• Involved in animal muscle contraction,
secretion, cell division and in plant greening
• Used in G-protein-linked and RTK pathways
• Ca2+ ions constantly pumped out of cytosol into
ECF, ER, mitochondria, & chloroplasts
▫ [Ca2+] in cytosol
▫ [Ca2+] in ECF, ER, mitochondria, & chloroplast
• Signal IP3 (or DAG)
stimulates release of
Ca2+ from ER activation of proteins
response
Response
• Cytoplasmic Responses: opening/closing of
ion channels in membrane, or change in cell
metabolism
▫ i.e.: epinephrine signals results in activation of
enzyme that catalyzes glycogen breakdown
• Nuclear Responses: genes may be turned
on/off that affect protein synthesis
▫ i.e. growth factor signal results in synthesis of
mRNA which will result in protein
Regulation of Response
• Signal Amplification: one signal causes large
response
• Specificity: different cells have different proteins
▫ i.e. signal, relay, & response proteins
• Efficiency: proteins are too large to diffuse
through cytoplasm; relay would be inefficient
▫ Scaffolding Proteins: hold many relay molecules in
same place to increase efficiency
• Termination: signal molecules bind reversibly
▫ When absent, receptor & relay molecules inactive &
able to do more work