Big Idea 3 Ch. 11 – Cell Communication Enduring Understanding 3.D (various Essential Knowledge topics are touched on here – provides an overview for material later)

Overview Take a moment and think of all the ways you can communicate to someone You can write things on paper, you can send an email, you could go on a social media site like facebook, etc. There are a few ways a cell can communicate: No distance Short distance Long distance

Contact - No distance Requires contact between 2 cells Example: Immune response an antigen (an invader) is sensed by a macrophage. Macrophage grabs the antigen and envelops it, uses a lysosome to chop it up, then releases it. Part of the antigen is carried to the surface. The macrophage passes the shape to the helper T cell (the protein inside the macrophage is called MHC2 links up to a protein on the helper T cell called CD4) and sends the shape of the antigen across the connection between the two cells The helper T cell is activated The macrophage leaves while the Helper T activates B cells to make antibodies and memory cells (humoral response), and Killer T cells which kill already infected cells (cell mediated response) Essential knowledge 3.D.2

Short Distance – Messages are sent short distances through a “local regulator” Neurons are a great example (when you prick your finger, a message is sent to your spinal cord, to your brain, and back) A message is sent from one neuron to another – but the neurons aren’t quite connected. We use a local regulator to make sure the message gets across. As message is sent from neuron A to neuron B, a chemical is released called a neurotransmitter which move across the synapse, or gap, which open up some channels and send the message on it’s way. (the chemical signals float across the gap between neurons – like an email sent from one cell to another) Why aren’t they just connected? We THINK that by opening it up, we get more control over how much of the signal gets through (or we can block it); endorphins are neurotransmitters that can actually block pain by breaking the connection Another example – quorum sensing in bacteria

Long distances – Long distance communication usually uses hormones to get the message across When you want to send a message throughout your body Hormones (a chemical) like growth hormones spread through your body Released from pituitary as you go through puberty; cells pick it up that allow muscles and bones to grow, all organs (but brain) grow, reduces liver uptake of glucose– there’s a whole list of things. All the cells in your body receive the message, but not all of them act on it If the message goes out of control then you get things like a “pituitary giant”

Evolution of Cell-Signaling Signal transduction pathways are a series of steps that convert signals on a cell’s surface into cellular responses Pathway similarities suggest that ancestral signaling molecules evolved in prokaryotes (cells with no nucleus) and have since been adopted by eukaryotes (cells with a nucleus)

Overview – The 3 stages of cell signaling *We’ll review each step in the cell signal process, then give an overview and examples of the signal transduction pathways Cells receiving signals go through three processes: Reception Transduction Response

Reception – receiving a signal

Reception: A signal molecule binds to a receptor protein, causing it to change shape The binding between a signal molecule (called a ligand) and receptor is highly specific A conformational change (change in shape) in a receptor is often the initial transduction of the signal Most signal receptors are found within the plasma membrane Some receptor proteins are intracellular, found in the cytosol or nucleus of target cells Small or hydrophobic chemical messengers can readily cross the membrane and activate receptors, some cannot (we’ll have an example of this later) 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

Transduction – transferring/relaying the message (multiple steps)

Transduction: Cascades of molecular interactions relay signals from receptors to target molecules in the cell 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 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 conformational (shape) change

Protein Phosphorylation and Dephosphorylation In many pathways, the signal is transmitted by a cascade of protein phosphorylations Phosphates enzymes remove the phosphates – or possibly add them (in this example, they are taking a phosphate group from ATP and turning it into ADP) This phosphorylation and dephosphorylation system acts as a molecular switch, turning activities on and off

Calcium ions – secondary messengers Calcium ions (Ca2+) act as a second messenger in many pathways (second messengers are molecules that relay messages from receptors on the cell surface to target molecules inside the cell, and they can also amplify the 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 a rise in the concentration of Ca2+ in the cytosol triggers many types of events such as: muscle contractions and activation of T and B cells

Response (regulation)

Response: Cell signaling leads to regulation of cytoplasmic activities or transcription 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 may involve action in the nucleus Many pathways regulate the activity or synthesis of enzymes or other proteins, usually by turning genes on or off in the nucleus

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

Review - video

Signal Transduction Pathways – the overview and examples Very important in the function of cells Think of an electric guitar – when the strings are vibrated, the electric pickup in the guitar (magnets and wires) transduce the message from the wires into a signal which transfers it to an amplifier which can make it really loud and you can hear it Signal transduction pathways do the same thing – starts with a message (in the form of a chemical) which is transduced into actions in the cell, which can then be amplified

Signal Transduction Pathways cont. They all work in basically the same way Two types : Protein modification Phosophorylation cascade (a phosphate group which carries energy will be passed off from one chemical to another to another until it eventually has an action).

Example – protein modification: A message comes in and is picked up by a receptor (on the membrane on the outside of the cell) It docks with the receptor and when it does that it changes the shape of the receptor (example – the G-Protein receptor) Then we have transduction, which changes the message (from a signal message outside the cell to a message inside the cell) We then use a secondary messenger (like cAMP – cyclic AMP – a very common messenger in cells – or Ca+) This eventually targets the cells (like in the liver, which release glucose from glycogen)

Example – phosphorylation cascade (Liver Cells and epinephrine) Epinephrine is a chemical messenger given off by your adrenal glands; it moves throughout your body, but especially affects cells in your liver The epinephrine is called a ligand (a chemical that can’t make it’s way through the hydrophobic layer of your membrane) It docks with a receptor – in this case a G-Protein receptor, which is embedded within the membrane. When the ligand docks onto the receptor protein, it causes a shape change in the protein (a conformational change) When the protein changes shape, it releases an alpha subunit (from the bottom portion of the protein, which is inside of the cell) which moves to another protein in the membrane called adenylyl cyclase Before the alpha subunit comes, adenylyl cyclase is an inactivated enzyme (it’s not working yet). Once the subunit is in place, it’s ready to do it’s job as an enzyme, which is to convert ATP into cAMP, which is a type of secondary messenger (basically ATP loses 2 phosphates and becomes a monophasphate); a cyclic portion (cyclic AMP) is also made, which act as messengers which spread throughout the cell These secondary messengers are going to target something called the protein kinase (which has two catalytic subunits which speed up chemical reactions, and two regulatory portions) When cAMP binds to the regulatory portions, it releases the catalytic potions which release a cascade of energy The catalytic potions will become phosphoralating, which means they’ll pick up portions of ATP and become activated They then can act on enzymes within the cell – in this case they’re going to drop off a phosphate to phosphorylase which will release glucose from glycogen in the cell