Molecular and Cell Biology II
Molecular and Cell Biology II B M B 252
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Date Created: 11/01/15
Lecture 1 Principles of cell communication How do cells communicate Cell signaling Important for development tissue homeostasis and repair immunity etc a What is cell signaling Most cells in multicellular organisms can emit and receive signals Signals are called extracellular signal molecules Receptor proteins bind the signal molecules Binding activates intracellular signaling pathway which leads to a change in cell behaivior Signaling pathway plasma membrane of target cell I l lNIRACELLULAR SIGNALIVN39G P39ROTEINS l O H eFrecxonthoIEINs metabolic gene regulatory cytoskeletal enzyme protein protein Figure 151 Molecular Biology of the Cell Garland Science 2008 Unicellular organisms also use signaling Bacteria respond to chemical signals secreted by their neighbors This process is called quorum sensing It can regulate aggregation motility biofilm formation spore formation sexual conjugation etc Yeast communication budding yeast cells responding to a mating factor Signal to mate pheromone Yeast are normally spherical Protrusion towards the divide by mitosis source of pheromone A Figure 152 Molecular Biology of the Cell Gartand Science 2008 Most signaling proteins and receptors were conserved in evolution Studies of yeast mutants unable to mate helped identify proteins involved in signaling These proteins have homologs in animal cells The number of proteins in animals greatly increased by gene duplications and divergence Animal proteins involved in signaling are grouped into families highly conserved in evolution Many of these proteins were first discovered in Drosophia fly and C elegans worm What is the signal There are hundreds of kinds of signaling molecules They include proteins small peptides amino acids Nucleotides steroids retinoids Fatty acids derivatives dissolved gases NO CO Signals can bind to cell surface receptor or diffuse through plasma membrane and bind inside the cell l l l plasma membrane cellsurface receptor protein hydrophilic signal molecule target cell Figure 153 Molecular Biology of the Cell Garland Science 2008 l l t l l m l l l t g small hydrophobic A signal molecule 0 O 0quot carrier protein target cell nucleus intracellular receptor protein Four forms of intercellular signaling A A WVSWEFEIIEE W signaling cell target cell Signaling cell 1 39 23 Short distance membrane local bole al mediator lawman C D IER EIEYQEIE endocrine cell receptor target cell synapse neuron lJI l39 hormone 39 3 Long distance axon target cell Q cell neurotransmitter body 7 bloodstream target cell Figure 154 Molecular Biology of the Cell Garland Science 2008 Communications over short distances m a m S i g n al i n g Signaling Gequot targetce Important in development and immune responses b Cells can extend long 332 9 processes can be molecule relatively long range Figure 15 4a Molecular Biology of the Cell Garland Science 2008 Communications over short distances signaling Signa39ing Paranear cell I 0 target gt cells Autocrlne Signaling when cell ets its own local I g mediator S39gna 3 Why is the signal localized quickly absorbed by other cells degrade very quickly lmmobiized in extracellular matrix Communications over long distances MWAWE signaling synapse neu ron L axon quot tar etce cell neurotransmitter g body 1 Neurotransmitters Synaptic I vesicle Neurotransmitter euptake pump Axon Voltage gated Ca ltermwnall channel quot 1 Neurm l transmitter receptors V S it me It Postsynaptic C39Ft 9 density r DEl39llJll39ltIC 1 spine Figure 1540 Molecular Biology of the Cell Garland Science 2008 Neuron gets activated by stimuli from other cells or environment Sends signal action potential along its axon Signal reaches the synapse Neurotansmitter is released Neurotansmitter binds to receptors on target cell process takes less than millisecond Communications over long distances Endo ms39de Signaling molecules here are hormones greek 13mm signaling Endocrine cells endocrine cell receptor secrete hormones Into distances through bloodstream to reach Lee 1 their target cells 7 bloodstream target cell Figure 15 4d Molecular Biology of the Cell Garland Science 2008 target cell the bloodstream hormone 1C9 Hormones travel long if 4n Comparison of longrange signaling mechanisms Endocrine Synaptic Slow Fast Relies on diffusion and blood flow Low concentration signal Hormones are low concentration in blood High affinity of receptors Electrical impulse 100 msec diffusion of neurotransmitter over less than 100 nm High concentration signal High concentration of neurotransmitter at synapse Low affinity of receptors neurotransmitter needs to dissociate rapidly The target cell can respond to a signal slow or rapidly extracellular signal molecule intracellular signaling 1 cellsurface pathway ALTERED PROTEIN FUNCTION FAST i lt sec to minsl c Figure 156 Molecular Biology of the Cell Garland Science 2008 An animal cell behavior depends on the combination of signals it receives Au 4 y quotx a k v V apoptotic 7 cell I 5 C No signals Figure 158 Molecular Biology of the Cell Garland Science 2008 Different cells respond differently to the same signal molecule Response to acetylholine A acetylcholine B lilil m E l 0 CH3 receptor II I proteln H3C c o CH2 CH2 N CH3 I gt gt CH3 C ELK tattl i ailjl acetylcholine 4 ll Figure 159 Molecular Biology of the Cell Garland Science 2008 For the fast and sharp response the intracellular signal should be rapidly removed when its no longerneeded Many extracellular signal molecules have short halflives some less than 10 min Many responses depend on conversion of intracellular signaling molecules from inactive to active form rather then synthesis and degradation Activation may be phosphorylation or GTP binding inactivation dephosphorylation or GTP hydrolysis to GDP Cells can share intracellular signaling molecules uoughgapjunc onsandrespondto extracellular signals in a coordinated way gap junction Example liver cells A signal of a low glucose level stimulates liver cells to 7 I break glycogen into 39 39 quot glucose The liver smaquot moecue cells share CAMP through gap junctions Can be Calcium ions or cAMP to work together Figure 157 Molecular Biology of the Cell Gartand Science 2008 The fate of the developing cells depends on concentration of the signal A signal molecule in development is called morphogen source of morphogen Means no dev program yet morphogen gradient 6 uncommitted Cells were initially cells the same v committed cells A B C Means they got the dev program depending on how much signal they got Figure 1510 Molecular Biology of the Cell Garland Science 2008 Signals can bind to cell surface receptor or diffuse through plasma membrane and bind inside the cell atmoatuma small hydrophobic A signal molecule 0 O 0 carrier protein plasma membrane cellsurface receptor protein target cell hydrophilic signal molecule target cell nucleus cellular receptor protein Figure 153 Molecular Biology of the Cell Garland Science 2008 Signals can bind to cell surface receptor or diffuse through plasma membrane and bind inside the cell Signal molecules Nitric oxide NO Carbon monoxide CO Steroid hormones Thyroid hormones Retinoids Vitamin D Figure 153 Molecular Biology of the Cell Ganand Science 2008 small hydrophobic signal molecule carrier protein target cell nucleus intracellular receptor protein Gas NO is a signal molecule in animals and plans NO relaxes smooth muscles in animals smooth muscle ells basal lamina Nerves release neurotransmitter acetylcholine Ach lumer Endothelial cell b39 quote 39 responds by releasing NO NO relaxes smooth muscle cells Blood vessel dilates Figure 1512a Molecular Biology of the Cell Garland Science 2008 Gas NO can lead to dilation of blood vessels Many types of nerves use NO as a neurotransmitter Made in cells from amino acid arginine by NO synthase NOS Can diffuse across the membrane in and out of the cells Acts locally since its lifetime is 510 sec Oxygen and water eventually convert it in nitrites and nitrates NO binds to active site of guanylyl cyclase activating it to produce other intracellular signaling molecule cyclic GMP cGMP relaxes smooth muscles and helps blood vessels dilate The drug nitroglycerine is converted into NO in the body It is used to prevent heart attack Cyclic GMP Relaxes smooth muscles NO T GTP CGMP O 0 N l NH NH 9 9 9 MM GWSB H gm HO P O P O P O N C2 0 lt5 5 5 o 0 0H HOPO EN H2 Ahodiestarase 5 o GMP Viagra Mechanism of relaxation of smooth muscle activated nerve terminal acetylcholine O NO bound to activated NO synthase NOS guanylyl cyclase Ilm arginine gt V No RAPID RELAXATION OF RAPID DIFFUSION OF P SMOOTH MUSCLE CELL N0 ACROSS MEMBRANES LAvuinin LC lllllinl NH7 Fm NH 0 Y 0 NH NH N kNH NADPH 02 N O ltN N NHZ H 02 o i1 poi H3N cun HJN cou V0 0 Cyclic guanosine monophosphate cGMP N I xynmasn PONFDE TerONT Practice questions What are the major components of a signaling cascade What is quorum sensing Which process in yeast requires signaling pathway Give examples ofthe molecules which can act as signals What is the difference between signals which bind to intracellular and cellsurface receptors What are the four forms of intercellular signaling What keeps the signal localized in paracrine signaling What are the differences between synaptic and endocrine signaling speed of signal delivery concentrations of signal affinity of receptors duration of signal What other factors determine the speed of cellular response What happens to the cell in the absence ofthe signals What kinds of cellular responses can acetylcholine stimulate What kind of molecules can pass through the gapjunctions and how is it important What is the type of signaling molecule which forms gradients in development What molecules can act as signals for intracellular receptors What kind of a receptors can NO bind cellsurface or intracellular Desciribe the action of NO on blood vessels What does NO bind to What is the function ofguanylyl cyclase phosphodiesterase Which ofthem is blocked by viagra Describe the mechanism of smooth muscle relaxation What is the mechanism of action ofthe drug nitroglycerine