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BIOL 130 Study Notes Unit VII Intracellular Compartments & Transport

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BIOL 130
Richard Ennis

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Unit 8 Cell Communication Why do Cells Need to Communicate with One Another? • For single celled organisms, communication is a means to be able to mate/reproduce • For multicellular organisms, cellular communication is used to coordinate: o Cell development o Growth (i.e. coordinating “whole body” growth and development with environment o Every day physiology Long vs. Short Range Communication of Animal Cells: • Signal molecules can be a variety of different molecules: proteins, peptides, amino acids, nucleotides, steroids, fatty acid derivatives, and even dissolved gases! • However, they all rely on only a small number of communication styles to relay messages across o Endocrine (i.e. hormones) – Long Distance; Public  Long range and very public style of communication  Involves endocrine cells sending the signal throughout the whole body  Done by secreting hormones throughout the blood stream (i.e. hormones)  The cells that produce these hormones are called endocrine cells (e.g. the pancreas) o Paracrine – Short Distance; Less Public  Short range and private style of communication  Signal molecules secreted by the signalling cell do not enter the blood stream  Instead, they diffuse through extracellular flood  Thus, they act as local mediators on other NEARBY cells  Sometimes cells can even respond to the local mediators that they themselves produce (autocrine signalling) – example: cancer cells o Neuronal – Long Distance; Private  Neuron cells, like endocrine cells, can deliver messages over long distances  The message however is not broadcasted widely, but is delivered very quickly and specifically to individual cells privately  Axons extend from the neuron towards a target  When activated by signals from the environment from nerve cells, electric signals sends electrical impulses along the axon (up to 100m/s)  Electrical impulse is then converted to a chemical form, where the electrical signal causes each nerve terminal to release a neurotransmitter  The neurotransmitter diffuses across the gap between the axon and the target cells called the synapse o Contact-Dependent – Short Distance; Very Private  The most intimate/private and most short-range style of communication  Does not require the release of a signalling molecule at all  Instead, cells make direct physical contact  Signalling molecules lodged in the plasma membrane of the signalling cell interact with the target cell’s receptor proteins embedded in its plasma membrane  Example: Contact-dependent signalling allowed adjacent cells to specialize to form different cells types! Signalling Pathways: The Step-wise Overview 1. Signalling molecules is synthesized and released by signalling cell 2. Signal molecule travels to target cell 3. Signal molecule binds to a receptor protein on/in the target cells o Causes signal transduction 4. Changes in protein activity (activation or inactivation) or gene expression subsequently occur 5. Results in a cellular response – changes in cell shape, movement, metabolism, etc. • In general, information is transmitted along a signalling pathway. o This step-wise pathway is best described as a series of steps that cause the members of a pathway to become activated or inactivated in sequence o Which ultimately results in changes to protein shape and activity Signal Molecule Release  Signal Molecule Travel  Reaches Target Cell  Changes in Protein Activity or Gene Expression  Changes in cell shape, movement, etc. The Same Signal Causes Different Responses Depending on the Target Cell: • The extracellular signal molecule alone is not the message • But rather the information conveyed to a target cell is dependent on how the target cell receives and interprets the signal o This is because the same signal molecule can cause different responses depending on the target cell, since different cells could be specialized differently • Example: Acetylcholine o In heart muscle cells, acetylcholine decreases rate and force of contraction o In salivary gland cells, it causes secretion o In muscle cells, it causes contraction! Cell Response Can Be Fast or Slow: • Length of time that a cell takes to respond to an extracellular signal can vary greatly o Depends on what needs to happen once the message has been received in order to ultimately change cellular behaviour • Fast Responses: Involves Simple Altering of Protein Activity o Some responses like muscle contraction can be very quick (i.e. seconds or minutes) o This is possible because in these cases, signal affects the activity of proteins and other molecules  These molecules are ALREADY present inside the target cell, and are simply awaiting signalling orders • Slow: Involves Changes in Gene Expression and Protein Synthesis o Examples like cell growth and division can take many hours after being triggered by a signalling molecule o This is because responses to these signals requires changes in gene expression and the production of new proteins via synthesis, which is much more lengthy and complex Locations of Receptors Can Usually Be Predicted by the Chemistry of the Signal Molecule: • Cell-surface receptors: o If a cell-surface receptor is present on the plasma membrane, chances are this receptor is meant for a signal that is HYDROPHILIC (likes water) o This makes sense because the signal molecule prefers the water in the extracellular environment  It is unable to cross the plasma membrane  Therefore, it will bind on the cell surface • Intracellular receptors: o These receptors are inside the cytosol or nucleus o They are meant for hydrophobic signal molecules o This makes sense because if it’s located within the cell, hydrophobic signals can get away from water by going through the plasma membrane to enter the cell. Small Hydrophobic Signal Molecules Enter the Cell and Regulate Gene Transcription: • These signal molecules are known as “hormones” • They are generally hydrophobic, allowing them to cross the plasma membrane to bind to signal receptors inside the cell o These protein receptors are evolutionarily related to the nuclear receptor superfamily of transcription regulators o Located on the nuclear envelope Extension from topic above: Steroid Hormone Mechanism of Action • Example: Cortisol o Cortisol is a steroid hormone that activates a transcription regulator (activate or repress) o It diffuses directly across the plasma membrane and binds to its receptor protein located in the cytosol  Causes shape change and activates receptor protein o As stated above, the receptor protein is a member of the nuclear receptor family of transcription factors  Means that the activated receptor, that carries cortisol, will move to the nucleus across the nuclear pore o It is then able to bind to a regulatory region of a target gene to activated or repress gene transcription • Cortisol in particular has its receptor protein in the cytosol o But other steroid hormones could have their receptor proteins within the nucleus, already bound onto the DNA molecule itself. Most Signals Bind to Receptors on the Plasma Membrane: • Vast majority of signal molecules are either too large or are hydrophilic o Therefore do not pass through the plasma membrane of the target cell. o Examples: proteins, peptides, small water-soluble molecules • Thus, these large or hydrophilic signal molecules must bind onto receptors on the plasma membrane • The process of signalling: o Large or hydrophilic signal molecule binds onto the receptor on plasma membrane o The transmembrane receptor detects the signal on the outside  It performs the primary signal transduction  It binds the extra cellular signal and generates new intracellular signals in response o The message is passed from one intracellular signalling molecule to another  Each activating or generating the next signalling molecule in the pathway o This occurs until an effector protein receives it:  If a metabolic enzyme receives it, then metabolism is altered as a result  If a cytoskeletal protein receives it, then the cell’s shape/movement is altered  If a transcription regulator receives it, then gene expression is altered Intracellular Signalling Cascade: • From the onset of primary transduction by the protein receptor that receives the extracellular signal, intracellular signals are relayed to intracellular signalling molecules mentioned before • These intracellular signalling molecules are components of the intracellular signalling pathways o They serve as “secondary messengers”  Means that they are non-protein molecules that relay signals from cell surface receptors to target molecules within the cell • Secondary messengers can perform one or more functions to pass the message: RTID o Relay  Pass the signal onward to help spread it throughout cell o Transduce/Amplify  Make the signal stronger so that a larger cellular response can be achieved using only a few signal molecules o Integrate  Receiving the signal from more than one intracellular signalling pathway and combine/integrate them before relaying the signal onward o Distribute  Pass the signal to more than one signalling pathway or effector protein  Creates branches in the information to evoke complex responses Intracellular Signal Molecules Acting as Molecule Switches: • Many of the so called “switch proteins” controlled by phosphorylation are protein kinases o Often organized into phosphorylation cascades o One protein kinases, activated by phosphorylation, will phosphorylate the next protein kinase in sequence • Diagram A: Signalling by Protein Phosphorylation: o When the signal detected, ATP will donate a phosphate to the protein allowing the protein to turn on  Protein kinase is used to transfer ATP’s phosphate group onto the signalling protein o When the protein wishes to turn off, it turns its signal off, causing the phosphate to unbind  Protein phosphatase removes the phosphate group from the signalling protein • Diagram B: Signalling by a GTP-binding protein (G-proteins) o The signalling protein uses GTP instead of ATP o When the signalling protein wants to be activated, it sends a signal out causing GTP to bind onto the protein o These signalling proteins, however, are special because they have intrinsic GTPase capabilities. o This means that when they want to turn off, they simply cleave one of the phosphates off of GTP, causing it to turn into GDP, thus making the protein shut off. o A more in-depth look at the specific structure of G-proteins will be considered when we get to G-protein coupled receptors Regulation of Proteins by Phosphorylation: • There are methods to regulate proteins that use phosphorylation as a means for signalling • Every time a protein is activated, every step in its activation process needs to be inactivated in order for regulation to be effective • Activity of protein regulated by phosphorylation depends on the balance between the activities of: o The protein kinases (which tack on the phosphate for activation) o The protein phosphatases (which remove the phosphate for inactivation) All cell-surface receptor proteins bind to an extracellular signal molecule and transduce its message into one or more intracellular signalling molecules. The receptors themselves, though, are split up into 3 main categories: 1. Ion channel-coupled receptors 2. G-protein coupled receptors 3. Enzyme-coupled receptors Class I: Ion Channel-Coupled Receptors: • Ion channel-coupled receptors open and close to allow the flow of ions in and out of the cell o The flow of ions (inward or outward) changes voltage across the mem
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