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Transcript
Cell Signaling 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 Local and Long-Distance Signaling Cells communicate by chemical messengers • Cell (gap) junctions that directly connect the cytoplasm of adjacent cells • direct contact, or cell-cell recognition Paracrine system • messenger molecules that travel only short distances Endocrine system: Hormones = long-distance signaling. • Chemical messengers secreted into vascular system transported to long-distance target Stages of Cell Signaling 1. 2. 3. 4. Reception Transduction Response Termination I. Reception: A signal 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 Receptors in the Plasma Membrane • Most water-soluble signal molecules bind to specific sites on receptor proteins in the plasma membrane • There are three main types of membrane receptors: 1. G protein-coupled receptor • 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 2. Receptor Tyrosine Kinases • membrane receptors that attach phosphates to tyrosines • A receptor tyrosine kinase can trigger multiple signal transduction pathways at once 3. Ligand-gated Ion Channels • A receptor acts as a gate • 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 Receptors • Some receptor proteins are intracellular, found in the cytosol or nucleus of target cells • Small or hydrophobic chemical messengers cross membrane and activate receptors • Ex: steroids & thyroid hormones • An activated hormone-receptor complex can act as a transcription factor, turning on specific genes II. Transduction: Cascades of molecular interactions relay signals from receptors to target molecules in the cell • • • • • • Signal transduction usually multi-step process Signal amplification: can often amplify a signal provide more opportunities for coordination and regulation of the cellular response relays are mostly proteins Signal Cascade: Like falling dominoes, once started all subsequent steps will occur At each step, the signal is transduced into a different form, usually a shape change in a protein Protein Phosphorylation and Dephosphorylation • In many pathways, the signal is transmitted by a cascade of protein phosphorylations • Protein kinases transfer phosphates from ATP to protein Small Molecules and Ions as Second Messengers • The extracellular signal molecule that binds to the receptor is a pathway’s “first messenger” • Second messengers are small, nonprotein, water-soluble molecules or ions that spread throughout a cell by diffusion • Second messengers participate in pathways initiated by G protein-coupled receptors and receptor tyrosine kinases • Cyclic AMP and calcium ions are common second messengers - Cyclic AMP (cAMP) is one of the most widely used second messengers - Adenylyl cyclase, an enzyme in the plasma membrane, converts ATP to cAMP in response to an extracellular signal • Calcium is an important second messenger because cells can regulate its concentration • A signal relayed by a signal transduction pathway may trigger an increase in calcium in the cytosol • Pathways leading to the release of calcium involve inositol triphosphate (IP3) and diacylglycerol (DAG) as additional second messengers Signal Amplification • Enzyme cascades amplify the cell’s response • At each step, the number of activated products is much greater than in the preceding step III. Cell specificity & Response • Different kinds of cells have different collections of proteins • These different proteins allow cells to detect and respond to different signals • Even the same signal can have different effects in cells with different proteins and pathways • Pathway branching and “cross-talk” further help the cell coordinate incoming signals • Ultimately, leads to regulation of cellular activities • may occur in cytoplasm or nucleus • Many regulate synthesis of enzymes or other proteins, usually by turning genes on or off in the nucleus ex: final activated molecule may function as a transcription factor ex: activation of enzyme ex: alters cell characteristics IV. Termination of the Signal • Inactivation mechanisms are an essential aspect of cell signaling • When signal molecules leave the receptor, the receptor reverts to its inactive state Types of Nervous Systems Nerve Net: series of interconnected nerve cells • Simplest form • No clustering of neurons • Neurons are interconnected • Excitation of 1 neuron results in coordinated excitiation Cephalization: Neurons clustered to anterior into sensory organs • Segmental = repeating patterns • central nervous system (CNS) consists of a brain and longitudinal nerve cords • The peripheral nervous system (PNS) is composed of nerves and ganglia Histology of Nervous Tissue (microscopic anatomy) Neurons - nerve cells 1. Cell body- like most cells --Focal point for outgrowth of neuron processes(extensions) • Nuclei - clusters of cell bodies in CNS • Ganglia - clusters of cell bodies in PNS 2. Dendrites -neuron processes(extensions) – Input Regions • Short, tapering, and branched • Electrical signals are conveyed as graded potentials (not action potentials) 3. Axon - neuron processes – Conducting region (convey signal) • Slender processes of uniform diameter arising from the hillock • Long axons are called nerve fibers • Usually 1 unbranched per neuron • Rare branches, if present, are called axon collaterals • Axon terminal = terminal boutoun – Transmits signal branched terminus of an axon Secretory Region - neurotransmitters (chemicals) • Tracts - bundles of axons in CNS • Nerves - bundles of axons in PNS Neuroglia = glial cells - supporting cells ,protection Segregate and insulate neurons In CNS - Astrocytes , Microglia, Ependymal , Oligodendrocytes In PNS - Satellite cells , Schwann -> myelin sheaths myelin sheath hillock Node of Ranvier (Cell Body) Multipolar Bipolar Unipolar Neurons have a membrane potential (Volts) •Electrical Potential (Difference in electrical charge) •Membrane is Polar •Cell potential usually -40 to -90 mV (minus because inside is more negatively charged) •Generated by differences in ion conc. (Na+ K+ , Cl-, protein anions A-) •Ion concentrations are changed by Na+ K+ pump Na+/K+ ATPase Membrane protein Functions: The Na/K-pump • Always on • Makes electrochemical gradient Outside + Inside - High Na+ outside High K+ inside etc Membrane Potential: Difference in charge or voltage Subtle detail: absolute charge cannot be measured, only difference can. So actually measuring both inside and out and the positive charge outside matters Cell is polarized Inside negative outside positive Resting Membrane Potential Inactive other than pumps (Time) • Pumps generate Resting membrane potential = charge of the cell resting = no channels open • Every time all other channels are closed and membrane returns to normal it is due to the pump • Signaling in neurons by Changes in Membrane Potential • Brief changes in membrane potential are due to changes in membrane permeability • Regulated ion channels – are Sometime open sometimes closed Graded Potentials: receptor potentials, generator potentials, postsynaptic potentials • Magnitude varies directly (graded) with stimulus strength • Decrease in magnitude with distance as ions flow and diffuse through leakage channels • Short-distance signals Changes in Potentials •The electrical signal of a neuron is spread using the depolarization of the membrane potential along the axon •Generated by Gated-Membrane Ion Channels (changes membrane permeability) Example: ach - Na+-K+ gated channel •Closed when no neurotransmitter Na+ cannot enter the cell K+ cannot exit the cell •Open when a neurotransmitter is attached to the receptor Na+ enters the cell K+ exits the cell Example: Na+ channel •Closed when the intracellular environment is negative Na+ cannot enter the cell •Open with electrical stimulus (potential changes) Na+ can enter the cell What happens when sodium channels open? Depolarization of membrane potential (inside becomes less neg) +++ +++ --- --Original concentrations restablished Hyperpolarization – opposite of depolarization when membrane becomes even more negative than usual Graded Potentials •Short-lived (become repolarized quickly), local changes in membrane potential •Decrease in intensity with distance (the further out the less change in charge) •Magnitude varies directly with the strength of the stimulus •Sufficiently strong graded potentials can initiate action potentials 1. 2. Must have the right voltage gated channels Must pass threshold (about 10-15mV above resting potential) Threshold +++ +++ --- --- -55 Excitatory Postsynaptic Potentials •EPSPs are graded potentials that can initiate an action potential in an axon •Use only chemically gated channels •Na+ and K+ flow in opposite directions at the same time •Postsynaptic membranes do not generate action potentials Graded Potential Inhibitory Synapses and IPSPs (inhibitory postsynaptic potentials) •Neurotransmitter binding to a receptor at inhibitory synapses: 1. Causes the membrane to become more permeable to potassium and chloride ions 2. Leaves the charge on the inner surface negative 3. Reduces the postsynaptic neuron’s ability to produce an action potential Also Graded Potential, but negative