Chapter 11: Cell Communication

Word Roots: liga- = bound or tied to trans- = across Ligand – a small molecule that specifically binds to a larger one. Transduction – the transmission of external signals and conversion of a message inside of the cell

Signal Transduction Pathways Local Signaling Direct contact Cell junctions Local Regulators Paracrine signaling Synaptic signaling Long Distance Signaling Hormones Nervous

Direct Contact Cell to cell recognition – embryonic development and immune respose

Evolution of Cell Signaling Yeast cells Identify their mates by cell signaling  factor Receptor Exchange of mating factors. Each cell type secretes a mating factor that binds to receptors on the other cell type. 1 Mating. Binding of the factors to     receptors induces changes      in the cells that     lead to their     fusion. New a/ cell. The nucleus of the fused cell includes all the genes from the a and a cells. 2 3 Yeast cell, mating type a mating type   a/ a Figure 11.2 Similar cellular communication in yeast (Fungi) and mammals even though the last common ancestor of these two groups of organisms lived over a billion years ago. Similarities have also been found between plants and bacteria.

Local Signaling Less specific Growth factors More Specific Growth factors stimulate local cells to grow and multiply. The signal can be sent to and received by multiple cells. Nerve cell triggers the secretion of a neurotransmitter – seen in animal nervous systems Less specific Growth factors More Specific Neurotransmitters

Long Distance Signaling Very Specific Target specific cells Hormones (endocrine signaling) Nerves – electrical transmission of impulses www.arikah.com Plants use long distance signaling – ex: growth regulators that travel is vessels – hormone ethylene, a gas that promotes fruit ripening and regulation of growth is small and can pass through cell walls. Mammilian hormone insulin, regulates sugar levels in the blood, is a large protein of a thousand atoms.

Three Stages of Cell Signaling Earl W. Sutherland – 1971 Signal Transduction Pathway for glycogen breakdown. Reception Target cell detects a signal molecule from outside the cell when a ligand binds to a receptor Transduction binding of signal molecule changes the shape of the receptor initiating transduction  sequence of changes in a series of molecules Response Transduced signal triggers a specific cellular response Ex: catalysis of enzyme, activation of genes, etc..

Three Stages of Cell Signaling http://pizaroscience.weebly.com/uploads/2/0/4/6/20462914/11_05cellsignaling_a.mpg

Step 1: Reception Receptor Protein (conformational change) Membrane Cytoplasm Nucleus Signal Molecule Ligand (highly specific) Small/hydrophobic Ex: steroid hormones Large/water soluble Ex: epinepherine

A hydrophobic ligand can readily cross the plasma membrane and bind to an intracellular receptor http://highered.mheducation.com/sites/9834092339/student_view0/chapter9/mechanism_of_action_of_lipid-soluble_messengers.html Testosterone acts as a transcription factor

Three Main Types of Plasma Membrane Receptors G-Protein Linked Receptor Tyrosine Kinases Ion Channel

Ex: Fight or Flight Response G-Protein Linked Ex: Fight or Flight Response Reception: Epinepherine targets liver and muscle cells Transduction: activates glycogen phosphorylase Response: break down glycogen into glucose http://learn.genetics.utah.edu/content/cells/cellcom/

G-Protein Linked Embryonic development, sensory reception, yeast mating factors, epinepherine, many other hormones and neurotransmitters GTP – guanosine triphosphate (a nucleiotide) GDP GTP Ligand binding  receptor shape change inactive G protein binds  GTP replaces GDP  activating the G protein Inactive G protein Adenylyl cyclase Sensory in humans such as vision and smell G-protein diseases – bacterial infections – cholera, pertussis (whooping cough), and botulism - make their victims ill by producing toxins that interfere with G-protein function 60% of medications exert their effects by influincing G protein receptors GTP GDP Pi Signal transduction pathway initiated Activated G protein dissociates from the receptor  binds to an enzyme and alters its activity  triggering the next step in the pathway G protein acts as GTPase  hydrolyzing GTP into inactive GDP  shutting down pathway when ligan is not present

Receptor Tyrosine Kinases Kinase – enzyme that catalyzes the transfer of a phosphate group Tyrosine kinase – membrane receptors that attach phosphates to the amino acid, tyrosine Regulates growth and reproduction Multiple pathways stimulated Branched pathways (10+) Abnormal receptor tyrosine kinases may contribute to some kinds of cancer

Receptor Tyrosine Kinases Example is a growth factor binding to a tyrosine kinase Dimerization activates the tyrosine kinase region of each polypeptide each tyrosine kinase adds a phosphate from ATP to a tyrosine amino acid on the tail of the other polypeptide

Ion Channel Receptors Ligand-gated ion channels Nervous system Sodium –Potassium Pump Some channels are controlled by electrical signals instead of a ligand Na+ and Ca2+ Na+ gates open during depolarization of a neuron Ca gates open when the impulse reaches it and the Ca influx causes the release of the neurotransmitters

Sodium Potassium Pump

Checkpoint Compare and contrast the three major types of membrane receptors.

Step 2: Transduction Multi-step Amplifies signal – signal sent to multiple molecules Require Relay Molecules Protein Kinases – transfers phosphate groups from ATP to a protein Serine/threonine kinases (animals, plants, fungi) Phosphorylation cascade Conformational change Increase or decrease activity of the protein Protein Phosphatases – remove phosphates from proteins Recycle and reuse kinases (dephosphorylation)

Reception Transduction Phosphorylation Cascade Response

Second Messengers Small, non-protein, water soluble molecules or ions Diffuse easily Easily Amplified Cyclic AMP (cAMP) Calcium ions (Ca2+) Inositol triphosphate (IP3) Diacylglycerol (DAG)

Cyclic AMP Cyclic adenosine monophosphate Created by Adenylyl Cyclase from ATP Many cAMP molecules – amplification Phosphodiesterase Activates Protein Kinase A

Cholera – a disease where water is contaminated with human feces Cholera – a disease where water is contaminated with human feces. Bacteria colonize in small intestines and produce a toxin. This toxin modifies the g protein that regulates salt and water secretion.G protein is unable to hydrolyze GTP into GDP and its stuck in its active form, continuously activating adenylyl cyclase to continue to make cAMP. An infected person develops severe diarrhea. Causes intestinal cells to continue to secret water.

‘Locking’ the pathway Cholera – Vibrio cholerae Locks G-Protein for water and salt regulation ‘on’ Unable to hydrolyze GTP into GDP = stuck in active form Diarrhea Vasodilatation Cyclic GMP – relaxes artery walls Viagra – blocks cyclic cGMP from breaking down into GMP – increases blood flow, prolonging the signal

Calcium Ions and Inositol Triphosphate Ca2+ low in cytosol, high in ER and ECF Active transport and membrane proteins Controlled by gated ion channels Regulates: Muscle contraction Secretion of other substances Cell division Used: G-protein Receptor Tyrosine Kinases

Step 3: Response Cytoplasmic or Nuclear Regulates: Enzyme/Protein activity Enzyme/Protein creation Transcription factors Growth factors Hormones

Cytoplasmic Response

Nuclear Response

Benefits of Transduction Pathways Signal Amplification Each step – more amplification Specificity Branched pathways – Receptor Tyrosine Kinases

Signaling Efficiency Scaffolding Proteins Signaling Complexes Proteins can participate in: More than one pathway in 1 cell Many pathways in different cells

Step 4: Signal Termination Reversible binding Signal molecule unbinds GTPase activity Phosphodiesterase Phosphatases