Cell Communication & Neural Signaling: Mechanisms & Receptors - PDF

Cell Communication Signal Transduction Mechanisms Why Do Cells Need to Communicate?  Ways Cells Communicate Cells communicate in several ways: – Directly through cell junctions – Electrical signals – Temporary cell-to-cell contact – Chemical signals  Cell Signaling ce...

Cell Communication Signal Transduction Mechanisms Why Do Cells Need to Communicate?  Ways Cells Communicate Cells communicate in several ways: – Directly through cell junctions – Electrical signals – Temporary cell-to-cell contact – Chemical signals  Cell Signaling cell signaling – Mechanisms by which cells communicate with one another Four main processes essential for cells to communicate 1. A cell sends a signal 2. Signal reception 3. Signal transduction 4. Response Chemical Signals and Cellular Receptors A Cell Sends a Signal In chemical signaling, a cell must synthesize and release signaling molecules Three types of signaling molecules: - Neurotransmitters - Hormones - Local regulators If the cells that can respond to the signal (target cells) are not nearby, the signal must be transported to them (usually by a circulatory system)  A Cell Sends a Signal Local regulators such as growth factors, can act on nearby cells Endocrine hormones (paracrine signals) are carried by the or on the cell that produces them bloodstream (autocrine signals)  Signal Transduction Signal transduction is the process by which a cell converts an extracellular signal into an intracellular signal, and relays the signal, leading to a cellular response Typically involves a chain of molecules that relay information  RESPONSES TO SIGNALS 1. Ion channels open or close -Example: Neurotransmitters excite or inhibit other neurons or muscle cells by affecting ion channels Enzyme activity is altered, leading to metabolic changes Example: Receptors on white blood cells (neutrophils) respond to peptides released by bacteria Specific gene activity may be turned on or off Example: Some steroid hormones bind to nuclear receptors and directly regulate gene expression  Reception of the Signal Receptors are large proteins or glycoproteins that bind with specific signaling molecules Many types of signaling molecules bind to receptors on the surface of the target cell, and do not enter the cell  RECEPTION Reception is highly specific process Ion channel–linked receptors G protein–linked receptors Enzyme-linked receptors Intracellular receptors  Receptors Cells are exposed to hundreds of types of signaling molecules – the signals a cell responds to depends on its receptors Cell-Surface and Intracellular Receptors A signaling molecule (ligand) binds to a specific receptor and triggers a biological response ❖ Hydrophilic molecules bind to protein receptors on the surface of target cells ❖ Hydrophobic molecules move through the plasma membrane and bind with intracellular receptors  Three Types of Surface Receptors (1) Ion channel-linked receptors (ligand-gated channels) – Found in the plasma membrane – Convert chemical signals into electrical signals – Ion channel opens or closes in response to binding of the signaling molecule (ligand) Example: acetylcholine (a neurotransmitter) binds to and opens a ligand-gated sodium ion channel Three Types of Surface Receptors 1- Ion Channel–Linked Receptor (2) G protein-linked receptors (G protein-coupled receptors) – Couple signaling molecules to signal transduction pathways inside the cell More than 400 G protein–linked receptors are potential targets for pharmaceutical interventions  First and second messenger Signaling molecule (first messenger) binds to G protein–linked receptor – Activates G protein – Activates adenylyl cyclase – Catalyzes formation of cAMP (second messenger) – Activates protein kinase – Phosphorylates proteins – Response in cell  G Protein–Linked Receptor (an abbreviation for Guanine-nucleotide binding protein) Transmembrane proteins with a binding site for a signaling molecule on the outside, and a binding site for a specific G protein that extends into the cytosol  G Protein-Linked Receptors G protein-linked receptors activate G proteins The signaling molecule acts as the first messenger, and information is relayed by the G protein to a second messenger First Messenger  second messengers – Ions or small molecules that amplify signals inside the cell and relay them to other signaling or target proteins – Produced in large quantities when receptors are activated – The last molecule in the signaling chain activates the final response Example: cyclic AMP Cyclic AMP Production  Cyclic AMP Activity Cyclic AMP activates protein kinase enzymes (such as protein kinase A) A protein is phosphorylated, its function is altered, and it triggers a chain of reactions leading to some response in the cell, such as a metabolic change  Adenylyl Receptor cyclase activated 2nd messenger Protein kinase A Protein Phosphorylated protein Alters some cell process -Opens or closes channels 3 -affects gene activity -Alters metabolism (3) Enzyme-linked receptors – Transmembrane proteins with a binding site for a signaling molecule outside the cell and an enzyme component inside the cell (Example: tyrosine kinases: that phosphorylate the amino acid tyrosine in proteins) – Bind hormones such as insulin and growth factors Enzyme-Linked Receptors in Plants – Ethylene Regulates seed germination and ripening of fruit  Enzyme-Linked Receptors - Signaling proteins bind to phosphorylated sites on receptor molecules, are phosphorylated, and can activate specific signaling pathways Activation of the last protein in the chain causes a specific cell response A Phosphorylation Cascade  Many Activated Intracellular Receptors are Transcription Factors Many intracellular receptors are transcription factors that regulate gene expression The ligand-receptor complex binds to a specific region of DNA and activates or represses specific genes Activated genes produce messenger RNA that carries the code for synthesis of a particular protein into the cytoplasm  Signaling molecules Intracellular 1 Signaling molecules pass through plasma Target cell Receptors membrane. 2 Signaling molecules Nucleus move through cytosol. 3 Signaling molecules pass through nuclear envelope and combine with Transcription factor receptor in nucleus. (Activated receptor) DNA 4 Activated receptor is a transcription factor that binds to Messenger and activates (or RNA represses) specific genes. Ribosome 5 Proteins are Messenger synthesized. RNA Protein 6 Cell activity is altered.  Signals must be terminated Signal termination – Returns the receptor and each of the components of the signal transduction pathway to their inactive states Examples: – After a G protein is activated, a subunit of the G protein (GTPase) catalyzes the hydrolysis of GTP to GDP – Cyclic AMP is inactivated by a phosphodiesterase, which converts it to adenosine monophosphate (AMP) Neural Signaling and Cells communication  Divisions of the Nervous system Central Nervous system (CNS) – Brain and spinal cord Peripheral Nervous system (PNS) – Neural tissue outside CNS – Afferent division brings sensory information from receptors – Efferent division carries motor commands to effectors Efferent division includes somatic nervous system and autonomic nervous system Functional Classification of Neurons  Neurons can be subdivided into three basic types based on function: 1) Sensory neurons / specialized for the detection of various types of stimuli; from various sensory receptors to the brain. 2) Motor neurons / transmit signals from the CNS to the muscles or glands. 3) Interneurons / process signals received from other neurons - connects motor and sensory neuron. Overview of nervous system functions. ( Schwann cells form the insulating myelin sheath around neurons of the peripheral nerves).  Neurotransmitters Must Be Inactivated Shortly After Their Release Neurotransmitters are removed from the synaptic cleft by two specific mechanisms: degradation into inactive molecules The enzyme acetylcholinesterase hydrolyzes acetylcholine into acetic acid (or acetate ion) and choline, neither of which stimulates the acetylcholine receptor. or neurotransmitter reuptak involves pumping neurotransmitters back into the presynaptic axon terminals or nearby support cells. The rate of neurotransmitter reuptake can be rapid; for some neurons/ millisecond. Some antidepressant drugs act by blocking the reuptake of specific neurotransmitters. For example, Prozac blocks the reuptake of serotonin, leading to a local increase in the level of serotonin available to postsynaptic neurons.