Chapter 11 Cell Communication AP Biology Adapted from

Chapter 11 Cell Communication AP Biology Adapted from Ms. Gaynor

External signals Cellular Responses • Cells use Signal transduction pathways – Convert signals OUTSIDE cellular responses • Similar in microbes and mammals, suggesting an early origin • http: //www. dnalc. org/resources/3 d/ cellsignals. html

Why do cells use chemical signals? • To communicate without physical contact • Communication distant can be small OR large Why study cell communcation? • Allows humans to modify and change pathways, create drugs to help diseases, control diseases, agriculture production, fruit ripening, etc. What happens when cells fail to communicate properly? • Abnormal development, diseases, cancer, death

Chemical Signals • Cells communicate through chemical messengers • Signal molecules (ligand) • growth factors • neurotransmitters • hormones (lipids) • peptides (small proteins) » Lipid soluble and insoluble

• In local (short distance) signaling, cells may communicate via direct contact Cell-cell recognition. Two cells in an animal may communicate by interaction between molecules protruding from their surfaces.

• Animal and plant cells – have cell junctions that directly connect the cytoplasm of adjacent cells Plasma membranes Gap junctions between animal cells Plasmodesmata between plant cells Both animals and plants have cell junctions that allow molecules to pass readily between adjacent cells without crossing plasma membranes.

Bacteria & Cell-to-Cell Communcation • Quorum sensing (short distance communication) – Bacteria secrete chemical signal helps bacteria coordinate behavior – Regulation of gene expression in bacteria in response to external stimuli. – Method used in response to population density

• Usually, multicellular organisms communicate using local regulators 2 types of Local signaling Electrical signal along nerve cell triggers release of neurotransmitter Target cell Secretory vesicle Local regulator diffuses through extracellular fluid Paracrine signaling. Secreting cell acts on nearby target cells by discharging molecules of a local regulator (i. e. growth factor) into extracellular fluid. Neurotransmitter diffuses across synapse Target cell is stimulated Synaptic signaling A nerve cell releases neurotransmitter molecules into a synapse, stimulating the target cell.

• In long-distance signaling – Both plants and animals use hormones Long-distance signaling Endocrine cell Blood vessel Hormone travels in bloodstream to target cells Target cell Animal Hormonal signaling Specialized endocrine cells secrete hormones into body fluids, often the blood. Hormones may reach virtually all body cells.

3 Stages of Cell Signaling • Earl W. Sutherland – Discovered how the hormone epinephrine acts on cells – http: //highered. mcgrawhill. com/olcweb/cgi/pluginpop. cgi? it=swf: : 535: : /sites/dl/free/00724 37316/120109/bio 48. swf: : Action%20 of%20 Epinephrine%20 on%20 a%2 0 Liver%20 Cell – Sutherland suggested that cells receiving signals went through 3 processes 1. Reception 2. Transduction 3. Response

• Overview of cell signaling EXTRACELLULAR FLUID Plasma membrane 1 Reception CYTOPLASM 2 Transduction 3 Response Receptor Activation of cellular response Relay molecules in a signal transduction pathway Signal molecule Figure 11. 5

STEP #1: Reception • A signal molecule binds to a receptor protein receptor changes shape • Binding between signal (called ligand) & receptor protein is highly specific » Changing shape initiates transduction of the signal

Receptors • Found in “target” cells • 2 types/ locations st 1 Type of Receptors 1. cell membrane (most abundant) called plasma membrane receptors

Plasma membrane receptors Chemical signal for these receptors can NOT pass THROUGH membrane…so it needs to be hydrophilic. WHY?

nd 2 type of Receptors 2. inside cell called intracellular receptors • Found in cytoplasm or nucleus • Chemical signal needs to pass THROUGH membrane…so it needs to be hydrophobic. WHY?

Intracellular receptors (con’t) • Signal molecules that are small or hydrophobic – WHY? ? ? – They can easily cross the plasma membrane • Ex: lipid soluble steriod/hormones (such as testosterone)

Specific Examples of Receptors Involved in Cell Communication

Example #1: Intracellular receptor – Ex: Steroid hormones Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein Hormonereceptor complex NUCLEUS The steroid hormone testosterone passes through the plasma membrane. 2 Testosterone binds to a receptor protein in the cytoplasm, activating it. 3 The hormonereceptor complex enters the nucleus and binds to specific genes. 4 The bound protein DNA m. RNA 1 New protein for MALE development stimulates the transcription of the gene into m. RNA. 5 The m. RNA is translated into a specific protein. Figure 11. 6 CYTOPLASM

• There are 3 main types of membrane receptors 1. G-protein-linked 2. Tyrosine kinases 3. Ion channel Names based on how they work!

1. G-protein-linked receptors • G-Protein = short for guanine nucleotide (GTP)-binding proteins – Ex: used in embryonic development, growth, smell, vision, over 60% of medications used today work by influencing G-protein pathways

G-protein-linked receptors • All G-protein-linked receptors have similar structure regardless of the organism in which they are found • Made of alpha-helices • Signal-binding site on outside of cell • G-protein-interacting site on inside of cell • http: //highered. mcgrawhill. com/sites/9834092339/student_view 0/chapter 9/signal_transduction _by_extracellular_receptors. html – Ex: epinephrine

2. Tyrosine kinase Receptor Signal-binding sitea Signal molecule Helix in the Membrane Tyrosines Tyr Tyr Tyr Receptor tyrosine kinase proteins (inactive monomers) CYTOPLASM Tyr Tyr Tyr Ex: used cell growth and development, reproduction Dimer Activated relay proteins Tyr Tyr P Tyr Tyr P P Tyr P 6 Activated tyrosinekinase regions (unphosphorylated dimer) ATP 6 ADP Fully activated receptor tyrosine-kinase (phosphorylated dimer) Inactive relay proteins Cellular response 1 Cellular response 2

• Part of the Tyrosine Kinase receptor on cytoplasmic side serves as an enzyme – Catalyzes transfer of Pi’s from ATP to amino acid Tyrosine on substrate http: //www. wiley. co m/college/fob/quiz/ quiz 21/21 -15. html

3. Ion channel receptors Signal Gate closed molecule (ligand) Ligand-gated ion channel receptor Ex: used in nervous system http: //highered. mcgrawhill. com/sites/0072495855/ student_view 0/chapter 2/an imation__receptors_linked_ to_a_channel_protein. html Ions Plasma Membrane Gate open Cellular response Gate close

STEP #2: Transduction (converting the signal) • Cascades of molecular interactions relay signals from receptors to target molecules in the cell • Multistep pathways – Can amplify a signal – Provide more opportunities for coordination and regulation

Signal Transduction Pathways • At each step in a pathway – signal is transduced (converted) into a different form USUALLY a conformational change in a protein using… – Protein Phosphorylation and Dephosphorylation

• In this process – A series of protein kinases add a phosphate to the next one in line, activating it • VERY IMPORTANT ~2% of our genes • Single cell has 100’s of different kinds of kinases (substrate specific) – Phosphatase enzymes then remove the phosphates

A phosphorylation cascade: like a Pi relay!! Signal molecule Receptor Activated relay molecule 1 A relay molecule activates protein kinase 1. Inactive protein kinase 1 ATP ADP PP ATP ADP Pi Active protein kinase 3 PP Inactive protein P 4 Finally, active protein kinase 3 phosphorylates a protein (pink) that brings about the cell’s response to the signal. ATP P ADP Figure 11. 8 Pi PP e Inactive protein kinase 3 5 Enzymes called protein phosphatases (PP) catalyze the removal of the phosphate groups from the proteins, making them inactive and available for reuse. 3 Active protein kinase 2 then catalyzes the phosphorylation (and activation) of protein kinase 3. ad sc ca Pi P Active protein kinase 2 on ati l ory ph os Ph Inactive protein kinase 2 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 Cellular response

Small Molecules and Ions act as Second Messengers • Second messengers – Are small, nonprotein, watersoluble molecules or ions Ex: c. AMP (cyclic AMP), Ca 2+, IP 3 http: //highered. mcgrawhill. com/sites/9834092339/student_view 0/ch apter 9/second_messenger__camp. html

Cyclic AMP • Cyclic AMP (c. AMP) – Is made from ATP by adenylyl cyclase (but c. AMP is short lived!) NH 2 O O O N N O P O P O Ch 2 O O N Adenylyl cyclase HO P O CH 2 O P P N N O Phoshodiesterase CH 2 O N N O O O P Pyrophosphate O O H 2 O O i OH OH ATP N N – O N NH 2 OH OH OH Cyclic AMP

• Many G-proteins – Trigger the formation of c. AMP, which then acts as a second messenger in cellular pathways First messenger (signal molecule such as epinephrine) G protein G-protein-linked receptor GTP ATP CAFFEINE BLOCKS c. AMP BY PHOPHODIESTERASE SO c. AMP LEVELS REMAIN HIGH Figure 11. 10 Adenylyl cyclase c. AMP Protein kinase A Cellular responses

Other Secondary Messagers… • Inositol triphosphate (IP 3) – Triggers increase in calcium ions in the cytosol by inducing the release of Ca+2 from the ER • Calcium (Ca+2) • Ex: involved in muscle contractions

1 A signal molecule binds 2 to a receptor, leading to activation of phospholipase C. EXTRACELLULAR FLUID 3 DAG functions as Phospholipase C cleaves a plasma membrane phospholipid called PIP 2 into DAG and IP 3. a second messenger in other pathways. Signal molecule (first messenger) G protein DAG GTP PIP 2 G-protein-linked receptor Phospholipase C IP 3 (second messenger) IP 3 -gated calcium channel Endoplasmic reticulum (ER) Cellular response (muscle contraction) Various proteins activated Ca 2+ (second messenger) 4 Figure 11. 12 IP 3 quickly diffuses through the cytosol and binds to an IP 3– gated calcium channel in the ER membrane, causing it to open. 5 Calcium ions flow out of the ER (down their concentration gradient), raising the Ca 2+ level in the cytosol. 6 The calcium ions activate the next protein in one or more signaling pathways.

STEP #3: Response • Cell signaling leads to: 1. regulation of cytoplasmic activities or 2. nuclear activities – Ex: transcription » DNA m. RNA » http: //highered. mcgrawhill. com/sites/9834092339/student_vie w 0/chapter 9/intracellular_receptor_mo del. html

• Cytoplasmic response to a signal Binding of epinephrine to G-proteinlinked receptor (1 molecule) Reception Transduction Signal Amplification Active G protein (10 molecules) • Each protein in a signaling pathway Inactive adenylyl cyclase – Amplifies Active adenylyl cyclase (10 ) (continues) signal ATP by activating Cyclic AMP (10 ) multiple copies of Inactive protein kinase A next component in Active protein kinase A (10 ) the pathway – Can be many or few Inactive phosphorylase kinase Active phosphorylase kinase (10 ) proteins in cascasde Inactive G protein 2 2 4 4 5 Inactive glycogen phosphorylase Active glycogen phosphorylase (106) Response Figure 11. 13 Glycogen Glucose-1 phosphate (108 molecules)

• Other pathways – Regulate genes by activating transcription factors that turn genes on or off Growth factor Reception Receptor http: //highered. mcgrawhill. com/sites/9834092339/stu dent_view 0/chapter 9/how_int racellular_receptors_regulate _gene_transcription. html Phosphorylation cascade Transduction CYTOPLASM Inactive transcription Active factor transcription factor P Response DNA Gene Figure 11. 14 NUCLEUS m. RNA

• Pathway branching and “cross-talk” – Further help the cell coordinate incoming signals Signal molecule Receptor Relay molecules Response 1 Cell A. Pathway leads to a single response Response 2 3 Cell B. Pathway branches, leading to two responses Activation or inhibition Figure 11. 15 Cell C. Cross-talk occurs between two pathways Response 4 Response 5 Cell D. Different receptor leads to a different response

Signaling Efficiency: Scaffolding Proteins and Signaling Complexes • Scaffolding proteins – Can increase the signal transduction efficiency igure 11. 16 Signal molecule Plasma membrane Receptor Scaffolding protein Three different protein kinases

Termination of the Signal • Signal response is terminated quickly – By the reversal of ligand binding INACTIVE- TURNED “OFF” ACTIVE- TURNED “ON”

When things go wrong… • Diabetes • Heart disease • Neurological or autoimmune disorders • Cancer • Death (ex: from neurotoxins, poisons, pesticides)

Great tutorial to use to study… • http: //www. biology. arizona. edu/CELL_BIO/ problem_sets/signaling/04 q. html