Cell Communication

The “Cellular Internet” All multicellular organisms must “communicate and cooperate” to maintain homeostasis universal mechanisms of cellular regulation involve cell-to-cell communication. Basically, a signal is received and then converted into a response within the cell

Methods used by Cells to Communicate Cell Signaling using chemical messengers (proteins, steroids, etc) Local signaling over short distances Cell-Cell Recognition Proteins attached to cell exterior; glycolipids and glycoproteins (e.g. blood type proteins) Local regulators (chem signals from the neighboring cells) Paracrine- secreted signal (e.g. growth factors) Synaptic- directed signal (e.g.neurotransmitter) Long distance signaling Hormones

Cell-Cell Communication Transport between cells cell junctions are protein tunnels directly connecting adjacent cells (called gap junctions in animal cells & plasmodesmata in plants); allow material to pass through (e.g. chem signals or water) Plasma membranes Plasmodesmata between plant cells Gap junctions between animal cells Figure 11.3 (a) Cell junctions. Both animals and plants have cell junctions that allow molecules to pass readily between adjacent cells without crossing plasma membranes.

Local Signaling Example: Cell-Cell Recognition Used to guard against unfamiliar cells and invaders; part of immune response Membrane bound cell surface molecules Glycoproteins Glyolipids Figure 11.3 (b) Cell-cell recognition. Two cells in an animal may communicate by interaction between molecules protruding from their surfaces.

Local Signaling Example: Local Regulators - Communicate with neighbors using local regulators, only work over a short distance - Paracrine signaling communicates with all cells surrounding (e.g. growth factor to stimulate mitosis near a wound) - Synaptic signaling is directed to one neighbor cell (e.g. neurotransmitters from one neuron to the next) (a) Paracrine signaling. A secreting cell acts on nearby target cells by discharging molecules of a local regulator (a growth factor, for example) into the extracellular fluid. (b) Synaptic signaling. A nerve cell releases neurotransmitter molecules into a synapse, stimulating the target cell. Local regulator diffuses through extracellular fluid Target cell Secretory vesicle Electrical signal along nerve cell triggers release of neurotransmitter Neurotransmitter diffuses across synapse is stimulated Local signaling

Long-distance Signaling Example: Hormones long-distance signaling used by both plants and animals; hormones (natural steroids) are released into bloodstream by glands and can go anywhere in the body causes changes in a lot of cells simultaneously (e.g. adrenaline) Hormone travels in bloodstream to target cells (c) Hormonal signaling. Specialized endocrine cells secrete hormones into body fluids, often the blood. Hormones may reach virtually all body cells. Long-distance signaling Blood vessel Target cell Endocrine cell Figure 11.4 C

Long-Distance Signaling Systems Nervous System (Animals only) Quick long distance communication through Electrical signals sent through neurons Endocrine System (Animals only) Glands that secrete hormones into cell spaces or into blood stream (lymph nodes, adrenal gland, pituitary gland, etc) Note: Plants also use hormones Transported through vascular system, plasmodesmata, or released into air (e.g. ripening fruit)

The Three Stages of Cell Signaling All cell signaling (long or short distance) occurs in three stages Reception – receive the signal Transduction – signal causes a cascade of communication inside the cell Response – cell responds to the signal Called Signal transduction pathways Note: Pathways are similar in all life, supporting evolution

Overview of cell signaling EXTRACELLULAR FLUID Receptor Signal molecule Relay molecules in a signal transduction pathway Plasma membrane CYTOPLASM Activation of cellular response Figure 11.5 Reception 1 Transduction 2 Response 3

Stage One: Reception EXTRACELLULAR FLUID CYTOPLASM Plasma membrane 1 1 Reception The receptor and signaling molecules fit together (lock and key model, induced fit model, just like enzymes!) Receptor Signaling molecule The signaling molecule (a ligand) binds to the specific receptor protein; shape determines function!

Stage Two: Transduction EXTRACELLULAR FLUID CYTOPLASM Plasma membrane 1 1 Reception 2 Transduction Receptor 2nd Messenger! Relay molecules in a signal transduction pathway Signaling molecule Reception sets off a relay team of communication proteins in the cell; second messengers carry the original exterior signal to the inside of the cell

Stage Three: Response EXTRACELLULAR FLUID CYTOPLASM Plasma membrane 1 Reception 2 Transduction 3 Response Receptor Activation of cellular response Relay molecules in a signal transduction pathway Can be catalysis, activation of a gene, triggering apoptosis, almost anything! Signaling molecule The cell will respond to the signal as directed (e.g. make a protein, produce more energy, enter mitosis, etc.)

Signal Transduction Animation http://media.pearsoncmg.com/bc/bc_campbell_biology_7/media/interactivemedia/activities/load.html?11&A http://www.wiley.com/legacy/college/boyer/0470003790/animations/signal_transduction/signal_transduction.htm

Common Receptor Proteins (stage one) G-protein coupled receptors Receptor tyrosine-kinases Ion channel receptors

G-Protein Coupled Receptors are often involved in diseases such as bacterial infections. G-Protein Receptors Inactive enzyme Plasma membrane G protein-coupled receptor Activated receptor Signaling molecule Enzyme GDP 1 2 GDP GTP CYTOPLASM G protein (inactive) Activated enzyme i GTP GDP P 3 4 Cellular response

Receptor tyrosine kinases Signal molecule Signal-binding site CYTOPLASM Tyrosines Signal molecule Helix in the Membrane Tyr Dimer Receptor tyrosine kinase proteins (inactive monomers) P Cellular response 1 Inactive relay proteins Activated relay proteins Cellular response 2 Activated tyrosine- kinase regions (unphosphorylated dimer) Fully activated receptor tyrosine-kinase (phosphorylated 6 ATP 6 ADP Figure 11.7

Ion Channel Receptors Very important in the nervous system Gate closed 1 Ions Very important in the nervous system Creates an action potential Signal triggers the opening of an ion channel Opening the channel allows ions to rush down a concentration gradient, creating an electrical signal from the moving charges Signaling molecule (ligand) Ligand-gated ion channel receptor Plasma membrane 2 Gate open Cellular response 3 Gate closed

Notes about Transduction Reminder, Transduction is the second stage. It occurs when cascades of molecular interactions relay signals from the receptor to the target molecules inside the cell It is a multistep pathway can amplify a signal and create a large response from a single ligand Requires communication and coordination within the cell itself Transduction Example: Protein Phosphorylation

Protein Phosphorylation and Dephosphorylation Protein Phosyphorylation cascade - An example of transduction in which a series of protein kinases add a phosphate to the next one in line, activating it, and sending the signal to the target (like a bucket brigade!) enzymes then remove the phosphates to reset the cascade after “Response” stage

A phosphorylation cascade Signal molecule Active protein kinase 1 2 3 Inactive protein kinase Cellular response Receptor P ATP ADP PP Activated relay molecule i Phosphorylation cascade P  A relay molecule activates protein kinase 1. 1 2 Active protein kinase 1 transfers a phosphate from ATP to an inactive molecule of protein kinase 2, thus activating this second kinase. Active protein kinase 2 then catalyzes the phos- phorylation (and activation) of protein kinase 3. 3 Enzymes called protein phosphatases (PP) catalyze the removal of the phosphate groups from the proteins, making them inactive and available for reuse. 5 Finally, active protein kinase 3 phosphorylates a protein (pink) that brings about the cell’s response to the signal. 4 Figure 11.8

Small Molecules and Ions as Second Messengers Transduction Example: Secondary messengers: small, nonprotein, water-soluble molecules or ions that act as secondary messengers to carry the signal to the target (example- cyclic AMP) (Note: Membrane Proteins would be the primary messengers since they get the signal first)

Cyclic AMP cAMP is often found with the G-protein receptors; made from ATP that has only one phosphate; secondary messenger ATP GTP cAMP Protein kinase A Cellular responses G-protein-linked receptor Adenylyl cyclase G protein First messenger (signal molecule such as epinephrine) Figure 11.10

Cyclic AMP Cyclic AMP (cAMP) Is made from ATP O –O N O P OH CH2 NH2 H2O HO Adenylyl cyclase Phoshodiesterase Pyrophosphate Cyclic AMP AMP i

Ex Diagram: Transduction in a G-protein pathway using cAMP Fig. 11-11 First messenger Adenylyl cyclase G protein G protein-coupled receptor GTP ATP Second messenger cAMP Ex Diagram: Transduction in a G-protein pathway using cAMP Protein kinase A Cellular responses

Second Messenger Example: Calcium Ions Calcium ions act as a secondary messenger in many different pathways because cells can regulate its concentration and location EXTRACELLULAR FLUID Plasma membrane ATP CYTOSOL Ca2+ pump Endoplasmic reticulum (ER) Nucleus Mitochondrion Key High [Ca2+] Low [Ca2+] Other secondary messengers trigger the release of concentration gradients of Ca2+ in various areas of the cell, creating moving charges and electrical signals. Pumps then reset the Ca2+ concentration gradient to be used again.

Calcium Ion Diagram example 3 2 1 IP3 quickly diffuses through the cytosol and binds to an IP3– gated calcium channel in the ER membrane, causing it to open. 4 The calcium ions activate the next protein in one or more signaling pathways. 6 Calcium ions flow out of the ER (down their con- centration gradient), raising the Ca2+ level in the cytosol. 5 DAG functions as a second messenger in other pathways. Phospholipase C cleaves a plasma membrane phospholipid called PIP2 into DAG and IP3. A signal molecule binds to a receptor, leading to activation of phospholipase C. EXTRA- CELLULAR FLUID Signal molecule (first messenger) G protein G-protein-linked receptor Various proteins activated Endoplasmic reticulum (ER) Phospholipase C PIP2 IP3 (second messenger) DAG Cellular response GTP Ca2+ (second messenger) IP3-gated calcium channel Figure 11.12

Cellular Response (Stage 3) Signaling molecule Cellular Response (Stage 3) Specificity of the signal The same signal molecule can trigger different responses depending on other signals and various receptor proteins or SMs Many responses can come from one signal! Receptor Relay molecules Response 1 Response 2 Response 3 Cell A. Pathway leads to a single response. Cell B. Pathway branches, leading to two responses.

The signal can also activate, inhibit ,or create multiple responses from one signal Activation or inhibition Response 4 Response 5 Cell C. Cross-talk occurs between two pathways. Cell D. Different receptor leads to a different response.

Response example- cell signaling leads to regulation of transcription (turn genes on or off)

Long-distance Signaling Response Example Some hormones induce transcription. Once inside the cell, the hormone attaches to a protein that takes it into the nucleus where transcription can be stimulated. (ex: testosterone, which is a transcription factor)

Termination of Communication Response is terminated quickly by the reversal of ligand binding

Any Questions?? Can You Hear Me Now?

Two body systems control MOST communication 1. Nervous System – uses ion concentration gradients and action potentials to communicate quickly through electrical impulses and neurons 2. Endocrine System - uses hormones secreted into the bloodstream (faster, further reach) or surrounding cell space; slower than nervous system, but longer lasting effect

Human Endocrine System

Major Vertebrate Endocrine Glands Their Hormones (Hypothalamus–Parathyroid glands) 36

Each system affects the output of the other Each system affects the output of the other. Feed back is another common feature. Neurosecretory cells in endocrine organs and tissues secrete hormones. These hormones are excreted into the circulatory system (ex. Adrenaline) or the surrounding cell space (ex. Lymph). 38

Stress and the Adrenal Gland Are the following hormone pathways Positive or Negative Feedback systems? Stress and the Adrenal Gland http://highered.mcgraw-hill.com/olcweb/cgi/pluginpop.cgi?it=swf::535::535::/sites/dl/free/0072437316/120109/bio48.swf::Action%20of%20Epinephrine%20on%20a%20Liver%20Cell

http://bcs.whfreeman.com/thelifewire/content/chp42/4202003.html 40

http://vcell.ndsu.nodak.edu/animations/regulatedsecretion/movie.htm 41

Answers Stress and Adrenaline – Positive Feedback (induces a response/change) Calcium and Blood Sugar regulation – Negative Feedback (prevents a change, maintains a normal level)