Cell Communication Notes Ex. Mating in Sacchromyces cerevisiae yeast Two types exist: a and α o a type make a factor signaling molecules, which bind to specific receptor proteins on nearby α cells while α make α factors that bind to receptors on a cells o Each cell responds to this by growing toward each other until the fusion (or mating) of two cells of opposite type occurs Ex. Quorem Sensing in bacteria Cells secrete small molecules that can be detected by other bacterial cells Allows them to monitor the density of cells around them = quorem sensing o Bacteria use it to coordinate behavior so they can perform activities that are only productive when performed by several cells in synchrony Ex. Biofilm = an aggregation of bacterial cells adhered to a surface for feeding Ex. Slimy coating on teeth in morning responsible for cavities LOCAL & LONG-DISTANCE SIGNALING Local Signaling includes: 1) Cell Junctions (Direct Contact) Signaling molecules dissolved in the cytosol can pass freely between adjacent cells Gap Junctions (animals) and Plasmodesmata (plants) 2) Cell-Cell Recognition (Direct Contact via membrane-bound surface molecules) Used in embryonic development and the immune response 3) Local Regulators Messenger molecules are secreted by the signaling cell Travel short distances and influence cells in the vicinity o Ex. Growth Factors in Animals = compounds that stimulate nearby target cells to grow and divide Numerous cells can simultaneously receive and respond to the molecules of growth factor produced by a single cell in their vicinity = paracrine signaling o Ex. Animal Nervous System Synaptic Signaling = an electrical signal along a nerve cell triggers the secretion of neurotransmitter molecules carrying a chemical signal These diffuse across the synapse (the narrow space between the nerve cell and its target cell), triggering a response in the target cell Long-Distance Signaling includes: 1) Hormones = chemical messenger molecules that are released by one cell that trigger a response in another (target) cell Ex. Ethylene = gaseous plant hormone that promotes fruit ripening o Why “one bad apple…” 2) Nervous System Electrical signal travels the length of a nerve cell and is converted back to a chemical signal when a signaling molecule is released and crosses the synapse to another nerve cell Converted back into an electrical signal, etc. THREE STAGES OF CELL SIGNALING The “Fight or Flight” Response Sutherland (1971) Investigated how epinephrine (a.k.a. adrenaline) stimulates the breaks down glycogen within liver and muscle cells o Glycogen glucose-1-phosphate glucose-6-phosphate (which can enter glycolysis and produce more ATP) o OR it can continue on to be converted into glucose fuels cells throughout the body Discovered that epinephrine stimulates glycogen breakdown by somehow activating Glycogen Phosphorylase o Adding epinephrine to a test tube of glycogen + cytosol no breakdown occurs o Adding epinephrine to a test tube of glycogen + cytosol + membrane fragments breakdown occurs Therefore, (1) epinephrine does NOT interact with the enzyme directly and (2) the membrane has some role in the process 1) RECEPTION = the target cell detects a signaling molecule coming from outside the cell Signaling molecule binds to a receptor protein located at the cell’s surface or inside the cell o Signaling molecule is complementary in shape to a specific site on the receptor molecule o Signaling molecule is the Ligand = a molecule that specifically binds to another molecule o Usually causes it to undergo a change in shape, which activates the receptor, enabling it to interact with other cellular molecules Plasma Membrane Receptors: o Most water-soluble (polar or ionic) ligands o Many diseases are due to malfunctions of these a) G-Protein Coupled Receptors (GPCR) Nearly 1000 exist in humans Works with G protein G protein is “off” when bound to GDP and “on” when bound to GTP o (See Diagram for details) Used by yeast mating factors, epinephrine responses, neurotransmitters, and many hormones Have roles in embryonic development and sensory reception Malfunctions responsible for illnesses, like cholera, pertussis, and botulism b) Receptor Tyrosine Kinases (RTKs) Kinase = enzyme that transfers a phosphate group from one molecule to another o (See Diagram for details) Abnormal function of these is related to many types of cancers c) Ligand-Gated Ion Channel Receptors Changes shape when ligand attaches, either opening or closing an ion channel Voltage-gated ion channels use electrical signals instead of ligands o Useful in nervous systems Intracellular Receptors: o Found in either the cytoplasm or nucleus of target cells o Usually signaling molecules for these are small and/or hydrophobic (can cross the hydrophobic barrier of the plasma membrane) Ex. Steroid hormones and thyroid hormones Ex. Testosterone only impacts cells with receptors for testosterone activates transcription factors for growth hormones that turn on specific genes for male sex characteristics in development 2) TRANSDUCTION = cascades of molecular interactions relay signals from receptors to target molecules in the cell Signal Transduction Pathway Usually includes activation of proteins by addition or removal of phosphate groups or release of other small molecules or ions that act as messengers Benefits include: o Ability to amplify a signal very quickly o Many opportunities to coordinate and regulate the pathway Many of the relay molecules in signal transduction pathways are protein kinases transfer phosphates from ATP to a protein o About 2% of our genes code for protein kinases o Most cytoplasmic protein kinases phosphorylate either of two other amino acids: serine or threonine (instead of tyrosine) o May create a “phosphorylation cascade” each phosphorylation event creates a change in shape of a molecule, which leads to either activation or deactivation of a step in the pathway Abnormal function of these can lead to cancer Equally important are protein phosphatases = enzymes that rapidly remove phosphate groups from proteins dephosphorylation o Make protein kinases available for reuse, allowing cell to respond again to an extracellular signal Second Messengers = small, non-protein, water-soluble molecules or ions that spread quickly throughout a cell by diffusion o Most common ones: cAMP and Ca2+ ions Cyclic AMP (cAMP) o Usually activates a serine/threonine kinase called protein kinase A o Protein kinase A usually then phosphorylates other various proteins, depending on cell type o Some G protein systems may inhibit adenlylyl cyclase inhibitory G protein Ex. Sutherland found epinephrine increases the amount of cAMP in the cytosol o Adenylyl cyclase converts ATP to cAMP in response to the epinephrine signal o Attachment of epinephrine triggers activation of adenylyl cyclase, which produces cAMP o Phosphodiesterase converts cAMP to AMP, deactivating it, so it is short-lived Ca2+ Ions o More widely used than cAMP as a second messenger o Used in both G protein and tyrosine kinase pathways o Concentration is usually low in cytosol, but is much higher in the E.R. In response to signals, second messengers are released: Inositol Triphosphate (IP3) and diacylglycerol (DA) Formed from cleavage of a certain kind of phospholipid in the plasma membrane IP3 triggers the release of Ca2+ from the ER 3) RESPONSE = Cell signaling leads to regulation of transcription or cytoplasmic activities The final activated molecule in a signaling pathway may: o Function as a transcription factor turns a gene “on” or “off” o Cause the opening or closing of an ion channel o Activate a specific enzyme o Regulate other cellular activities, like rearrangement of the cytoskeleton