Unit 4 Cell Communication AP Biology Ms Day

Unit #4: Cell Communication AP Biology Ms. Day https: //www. youtub e. com/watch? v=g. J dj. Gr. IGXDI https: //www. youtub e. com/watch? v=Fk k. K 5 l. Tm. BYQ

External signals Cellular Responses • Cells use Signal transduction pathways – Convert signals OUTSIDE cellular responses • Similar in microbes and mammals, suggesting an early origin

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 (proteins) • neurotransmitters • hormones (proteins or lipids) • peptides (small proteins) » Lipid soluble and insoluble » https: //www. youtube. com/watch? v=89 W 6 u. ACEb 7 M (14 min)

• 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 concentrates helps bacteria coordinate behavior – Regulation of gene expression in bacteria in response to external stimuli. – Method used in response to population density http: //ed. ted. com/les sons/how-bacteriatalk-bonnie-bassler

• 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 • https: //www. dnatube. com/video/1162 /Signal-transduction • https: //www. youtube. com/watch? v=Ft. Vb 7 r 8 a. Hco • Cells receiving signals go through 3 processes 1. Reception 2. Transduction 3. Response

• Overview of cell signaling http: //www. dnatube. com/video/233/The-Signal-Transduction-Pathway EXTRACELLULAR FLUID Plasma membrane 1 Reception 2 Transduction CYTOPLASM 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

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 (lipid soluble) http: //highered. mheducation. c om/sites/98340 92339/student _view 0/chapter 9/mechanism_ of_action_of_li pidsoluble_messe ngers. html 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 • Ligand-binding site on outside of cell • G-protein-interacting site on inside of cell • http: //highered. mheducation. com/sites/9834092339/student_view 0/cha pter 9/membranebound_receptors__g_proteins__and_ca 2__channels. html

G-protein-linked receptors – Specific Example = epinephrine • http: //highered. mheducation. com/olcweb/cgi/pluginpop. cgi? it=swf: : 535: : /sites/dl/free/0072437316/12010 9/bio 48. swf: : Action%20 of%20 Epinephrine%20 on%20 a%20 Liver%20 Cell

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 forms Activated relay proteins Tyr Tyr P Tyr Tyr P P Tyr P 6 ATP 6 ADP Activated tyrosinekinase regions (unphosphorylated dimer) 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 https: //www. youtub e. com/watch? v=Ob rs. Ql-v. PA 4

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/stu dent_view 0/chapter 2/animatio n__receptors_linked_to_a_cha nnel_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 – 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) • Think: “be kind” and give Pi’s – Phosphatase enzymes then remove the phosphates – https: //www. youtube. com/watch? v=CCDa 9 L 7 k. Y 24

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 Active protein kinase 1 o ph os Ph PP Inactive protein kinase 3 Enzymes called protein 5 phosphatases (PP) catalyze the removal of the phosphate groups from the proteins, making them inactive and available for reuse. Active protein kinase 2 3 then catalyzes the phosphorylation (and activation) of protein kinase 3. ATP ADP Pi Active protein kinase 3 PP Inactive protein P Finally, active protein 4 kinase 3 phosphorylates a protein (pink) that brings about the cell’s response to the signal. ATP P ADP Figure 11. 8 P i PP de ca as Pi P Active protein kinase 2 c on ADP ryl ATP ati Inactive protein kinase 2 Active protein kinase 1 2 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) – 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 INHIBITING 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 to a receptor, leading to activation of phospholipase C. EXTRACELLULAR FLUID 2 3 DAG functions as a second messenger in other pathways. Phospholipase C cleaves a plasma membrane phospholipid called PIP 2 into DAG and IP 3. 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/student_vie w 0/chapter 9/how_intracellular_recepto rs_regulate_gene_transcription. html NOTE: Transcription is DNA m. RNA 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)

Overall Signal Transduction Pathway…explained • https: //www. youtube. com/watch? v=q. OVke dx. Dq. Qo&feature=youtu. be

Evolutionary Significance of Cell Communication • https: //www. youtube. com/watch? v=Fs. Gwg i. Iv_NU&feature=youtu. be

Effects of Changes in Pathways • https: //www. youtube. com/watch? v=W 48 G k 2 Om 3 w. I&feature=youtu. be

Great tutorial to use to study… • https: //www. youtube. com/watch? v=q. OVke dx. Dq. Qo&feature=youtu. be • http: //www. biology. arizona. edu/CELL_BIO/ problem_sets/signaling/04 q. html

Cholera • Affects a G linked protein reception in the cells lining the intestines • Toxin from contaminated water causes this • Turns ON the signal permanently – (c. AMP) not broken down • Causes water imbalance leads to diarrhea and perhaps DEATH!!!