AP Biology – Ms. Whipple BCHS The yeast, Saccharomyces cerevisiae, has two mating types, a and Cells of different mating types locate each other via secreted factors specific to each type 1. Exchange of mating factors a 1 2. Mating 3. New a/ cell a a/ A signal transduction pathway is a series of steps by which a signal on a cell’s surface is converted into a specific cellular response Signal transduction pathways convert signals on a cell’s surface into cellular responses Pathway similarities in plants & bacteria suggest that ancestral signaling molecules evolved in prokaryotes and were modified later in eukaryotes The concentration of signaling molecules allows bacteria to sense local population density – Quorum Sensing Quorum Sensing allows bacterial populations to coordinate their behaviors so that they can carry out activities that are only productive when performed by a given number of cells in synchrony. One example of this is a Biofilm, an aggregation of bacterial cells that derive nutrition from the surface they are on. (a) Cell junctions Gap junctions between animal cells (b) Cell-cell recognition Plasmodesmata between plant cells In many cases, animal cells communicate using local regulators, messenger molecules that travel only short distances The ability of a cell to respond to a signal depends on whether or not it has a receptor specific to that signal. No Receptor = No Response Electrical signal along nerve cell triggers release of neurotransmitter. Local signaling Target cell Secreting cell Local regulator diffuses through extracellular fluid. (a) Paracrine signaling Secretory vesicle Neurotransmitter diffuses across synapse. Target cell is stimulated. (b) Synaptic signaling Endocrine cell Hormone travels in bloodstream. In long-distance signaling, plants and animals use chemicals called hormones Blood vessel Target cell specifically binds hormone. (c) Endocrine (hormonal) signaling Epinephrine stimulates the breakdown of Glycogen in liver and muscle cells. This is useful during a “fight or flight” response because it gives immediate energy to muscles for fighting or fleeing. 1. 2. Epinephrine does not interact directly with the enzyme responsible for glycogen breakdown; an intermediate step or series of steps must be occurring inside the cell. The plasma membrane is somehow involved in transmitting the signal. EXTRACELLULAR FLUID 1 Reception Receptor Signaling molecule CYTOPLASM Plasma membrane A signaling molecule binds to a receptor protein, causing it to change shape. The binding between a signal molecule (ligand) and receptor is highly specific A shape change in a receptor is often the initial transduction of the signal Most signal receptors are plasma membrane proteins EXTRACELLULAR FLUID 1 Reception CYTOPLASM Plasma membrane 2 Transduction Receptor Relay molecules in a signal transduction pathway Signaling molecule Cascades of molecular interactions relay signals from receptors to target molecules in the cell. The molecules that relay a signal from receptor to response are mostly proteins Like falling dominoes, the receptor activates another protein, which activates another, and so on, until the protein producing the response is activated At each step, the signal is transduced into a different form, usually a shape change in a protein Signal transduction usually involves multiple steps Multistep pathways can amplify a signal: A few molecules can produce a large cellular response Multistep pathways provide more opportunities for coordination and regulation of the cellular response EXTRACELLULAR FLUID 1 Reception CYTOPLASM Plasma membrane 2 Transduction 3 Response Receptor Activation of cellular response Relay molecules in a signal transduction pathway Signaling molecule Cell signaling leads to regulation of transcription or cytoplasmic activities The cell’s response to an extracellular signal is sometimes called the “output response” Ultimately, a signal transduction pathway leads to regulation of one or more cellular activities The response may occur in the cytoplasm or in the nucleus Many signaling pathways regulate the synthesis of enzymes or other proteins, usually by turning genes on or off in the nucleus The final activated molecule in the signaling pathway may function as a transcription factor Figure 11.15 Growth factor Reception Receptor Phosphorylation cascade Transduction CYTOPLASM Inactive transcription factor Active transcription factor P Response DNA Gene NUCLEUS mRNA Other pathways regulate the activity of enzymes rather than their synthesis Signaling pathways can also affect the overall behavior of a cell, for example, changes in cell shape Figure 11.17 RESULTS formin Fus3 Wild type (with shmoos) CONCLUSION 1 Mating factor activates receptor. Mating factor G protein-coupled Shmoo projection forming receptor Formin P Fus3 GDP GTP 2 G protein binds GTP and becomes activated. Fus3 Actin subunit P Phosphorylation cascade Fus3 Formin Formin P 4 Fus3 phosphorylates formin, activating it. P 3 Phosphorylation cascade activates Fus3, which moves to plasma membrane. Microfilament 5 Formin initiates growth of microfilaments that form the shmoo projections. A Receptor for that signaling factor!! A molecule that specifically binds to another molecule. For example, a signaling factor binding with a receptor causing a shape change and cellular response. Cell Surface proteins make up 30% of all human proteins but only 1% have been examined by x-ray crystallography. G protein-coupled receptors (GPCRs) are the largest family of cell-surface receptors A GPCR is a plasma membrane receptor that works with the help of a G protein The G protein acts as an on/off switch: If GDP is bound to the G protein, the G protein is inactive Figure 11.7b G protein-coupled receptor Plasma membrane Activated receptor 1 Inactive enzyme GTP GDP GDP CYTOPLASM Signaling molecule Enzyme G protein (inactive) 2 GDP GTP Activated enzyme GTP GDP Pi 3 Cellular response 4 Receptor tyrosine kinases (RTKs) are membrane receptors that attach phosphates to tyrosines A receptor tyrosine kinase can trigger multiple signal transduction pathways at once Abnormal functioning of RTKs is associated with many types of cancers Figure 11.7c Signaling molecule (ligand) Ligand-binding site helix in the membrane Signaling molecule Tyrosines CYTOPLASM Tyr Tyr Tyr Tyr Tyr Tyr Receptor tyrosine kinase proteins (inactive monomers) 1 Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Dimer 2 Activated relay proteins 3 Tyr Tyr P Tyr Tyr P P Tyr Tyr P Tyr Tyr P Tyr Tyr P P Tyr Tyr P Tyr Tyr P Tyr Tyr P P Tyr Tyr P 6 ATP Activated tyrosine kinase regions (unphosphorylated dimer) 6 ADP Fully activated receptor tyrosine kinase (phosphorylated dimer) 4 Inactive relay proteins Cellular response 1 Cellular response 2 A ligand-gated ion channel receptor acts as a gate when the receptor changes shape When a signal molecule binds as a ligand to the receptor, the gate allows specific ions, such as Na+ or Ca2+, through a channel in the receptor Intracellular receptor proteins are found in the cytosol or nucleus of target cells Small or hydrophobic chemical messengers can readily cross the membrane and activate receptors Examples of hydrophobic messengers are the steroid and thyroid hormones of animals An activated hormone-receptor complex can act as a transcription factor, turning on specific genes Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein DNA NUCLEUS CYTOPLASM Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein Hormonereceptor complex DNA NUCLEUS CYTOPLASM Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein Hormonereceptor complex DNA NUCLEUS CYTOPLASM Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein Hormonereceptor complex DNA mRNA NUCLEUS CYTOPLASM Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein Hormonereceptor complex DNA mRNA NUCLEUS CYTOPLASM New protein Probably on the Plasma Membrane because hydrophilic (water soluble) molecules cannot easily get through the phospholipid bilayer. Possibility of greatly amplifying signal!!