Cell Communication Chapter 11 p

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 H 2 O-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 +, Ca 2+ ) ▫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)  Ca 2+ Ions & IP 3

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

Ca 2+ Ions & IP 3 Involved in animal muscle contraction, secretion, cell division and in plant greening Used in G-protein-linked and RTK pathways Ca 2+ ions constantly pumped out of cytosol into ECF, ER, mitochondria, & chloroplasts ▫ [Ca 2+ ] in cytosol ▫ [Ca 2+ ] in ECF, ER, mitochondria, & chloroplast Signal IP3 (or DAG) stimulates release of Ca 2+ 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