Module 26: Types of Signal Molecules PDF

MODULE 26 Types of Signal Molecules Signals direct cell fate. Most cells depend on specific signals to survive; in the absence of these signals, cells die. Different cells require different combinations of survival signals; each cell type is restricted to different environments....

MODULE 26 Types of Signal Molecules Signals direct cell fate. Most cells depend on specific signals to survive; in the absence of these signals, cells die. Different cells require different combinations of survival signals; each cell type is restricted to different environments. Dependent on their receptors, cells respond differently to the same signal: acetylcholine stimulates the contraction of skeletal muscle cells but decreases the contraction of heart muscle cells. A signal molecule binding to identical receptors can produce different responses in different cells because the internal signaling pathways differ. Survive, Divide, Differentiate, Die Forms of Intercellular Signaling Cell-Contact Mode: Ligands bound to the surface of one cell influence a target cell with cell-surface receptors. Endocrine Signaling: Secreted ligands may act on distant targets (e.g., via hormones). Paracrine Signaling: Secreted ligands may affect cells in the immediate environment of the signaling cell (via local mediators). Synaptic Signaling (Nerve Mode): Neurons transmit signals electrically along axons and release signaling molecules (neurotransmitters) at synapses. Autocrine Signaling: Cells send signals to themselves; autocrine signaling is utilized in development. Contact-Dependent Signaling Through cell-surface molecules bound to the plasma membrane of the signaling cell, this is a direct interaction with cell-surface receptors on target cells. Through gap junctions (channels) connecting the cytoplasm of neighboring cells, allowing the passage of ions and small molecules. MODULE 26 What Is Signal Transduction? Signaling is typically transmitted from a receptor in the plasma membrane across the cytoplasm to subcellular compartments. The simplest model involves a chain of intracellular mediators regulating each other until the target is reached, interacting via interaction domains. In reality, there are branching networks, and the network of signaling molecules linking the receptor to intracellular targets (effector proteins) is called a signal transduction pathway or cascade. These pathways differ between cells, leading to different biological responses. First Messengers (Ligands) Molecules that signal between cells. Secreted by exocytosis, released by diffusion through the plasma membrane, or bound to the signaling cell surface. Target cells respond via receptors, mostly transmembrane proteins, though some receptors are inside the target cell, where small/hydrophobic signal molecules activate them. Intracellular signaling molecules (second messengers) and proteins are involved. Second Messengers Small molecules engaged in intracellular signaling. Their concentrations change rapidly to amplify signals (e.g., Ca2+ is released in large quantities in response to a signal and diffuses rapidly). If a rapid, generalized response is necessary, a second messenger is likely involved Some second messengers diffuse through the cytosol, while others, like diacylglycerol, are lipid- soluble and diffuse in the plasma membrane. MODULE 26 Molecules in the Signaling Cascade Relay Proteins: Pass the message to the next signaling component. Messenger Proteins: Carry the signal from one part of the cell to another. Adaptor Proteins: Link one signaling protein to another. Amplifier Proteins: Enzymes or ion channels that increase the signal by producing many intracellular mediators or activating many downstream proteins. Transducer Proteins: Convert the signal into a different form. Integrator Proteins: Receive signals from two or more pathways and integrate them before relaying the signal onward. Latent Gene Regulatory Proteins: Activated at the cell surface and migrate to the nucleus to stimulate gene transcription. Scaffold Proteins: Organize groups of interacting signaling proteins into complexes. Molecular Switches in Signaling molecular switch is a molecule that switches from an inactive to an active state until a process/signal switches it off proteins are phosphorylated and dephosphorylated by a kinase and phosphatase, respectively; the serine/threonine kinases are the most common types of protein kinases kinase cascade is a chain with several kinases, each activated by phosphorylation and then phosphorylating the next kinase GTP-binding proteins switch to an active state when GTP is bound and an inactive state when GDP is bound the phosphorylated state is not always the active state phosphorylation occurs only at specific Tyr, Thr, and Ser residues, depending upon the context (histidine is not phosphorylated in animals) MODULE 26 More on the Phosphorylation/Dephosphorylation Switch phosphorylation/dephosphorylation is the most common switch mechanism it is rapid compared to allosteric binding, it is more universal: tyrosine, serine, and threonine residues are in all proteins, whereas allosteric modulators have to be unique for each protein unlike serine/threonine phosphatases, tyrosine phosphatases remove phosphate groups from selected phosphotyrosines phosphorylation can induce a protein conformational change or provide a docking site for a protein Nuclear Receptors Retinoids, steroid, and thyroid hormones: small, hydrophobic, diffusing across the plasma membrane; soluble for transport in the blood by carrier proteins. Activated receptors bind to DNA to regulate gene transcription. Some nuclear receptors are activated by intracellular metabolites, not by secreted signals. Some receptors are in the cytosol and enter the nucleus after ligand binding. Thyroid and retinoid receptors are bound to DNA even in the absence of ligand; ligand binding alters the receptor conformation, causing a pre-existing inhibitory complex to dissociate. Putting It All Together Depending on the distance at which a ligand operates, signaling can be paracrine, endocrine, contact- dependent, or synaptic. Autocrine signaling is rare. Some signal molecules pass through the plasma membrane to activate intracellular receptors, which regulate the transcription of specific genes. Most extracellular ligands are hydrophilic and activate receptors on the cell surface. These receptors then relay the extracellular signal into intracellular pathways. There are three main families of cell-surface receptors: ion-channel-linked receptors, G-protein-linked receptors, and enzyme-linked receptors. Both enzyme-linked and G-protein-linked receptors pass signals through networks of intracellular proteins. Some signaling proteins act as molecular switches, becoming transiently activated by phosphorylation/dephosphorylation or GTP binding.