Cell CommunicationChapter 11p. 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 G-protein-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