chapter 6 BME3403 EABS
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This 9 page Class Notes was uploaded by Kathleen Quijada on Friday February 27, 2015. The Class Notes belongs to BME3403 EABS at Florida International University taught by Dr.Brown in Fall2015. Since its upload, it has received 79 views. For similar materials see Engineering analysis of biological systems EABS in Biomedical Sciences at Florida International University.
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Date Created: 02/27/15
tadbmx C We ducal 9 bl fl ln all 1 hrs xa lvum hmer in MM Tlrc Dull W nloravm of in N gymplay im l 33 pmf in 39 Couptcl rcuepfm wlcnpjmef w Mul39l39if li OwedQ Overview of Cell to Cell Communication j Autocrine amp Paracrine local signaling Endocrine system distant diffuse target Gap junction local Nervous system fast specific distant target W i Wok gtluch on 0 WY 5 C nal M MW r not b PUnuobLt H KL cut iiiomb V39atUL gt 1 1 aka v TInwLC ijiu a ownh uyi L406 if tramcc sa sis About this Chapter How cells communicate Electrical and chemical signals Receptor types and how they function Local regulation of cells Modification of receptors and signals Homeostatic balance depends on communication Feedback regulates integration of systems Fitaging J 4 Sm lt15 Mimi peph aLu QKS am m5 r 1 1 t 5 i A N0 C04 P Jaef Gap Junctions and CAMS a Gap iunctions lorrn UerCl Cytoplasmic connections between adgacenl cells 39 Protein channels connexin Direct flow to neighbor X mg 13 Jul Electrical ions charge Signal chemicals b Contactdependent signals 0 x o h cu DH CAMS sgrigaaszioisgzmizsm two cells Need direct surface contact Signal chemical Cf 7 MaltaUs fLoLJL Cil eprpdu ca m 0N Off a n HCc OWE an bmH l LU 0 loo can C2 Mg bgl s m i iWDcE 3 15pr S39QKQL iU b1in w mi gvi g ummsuigvmom x I Rolling Endotinelial activation C aQRSion m mm Leukocyte activation Chemotaxis activation FIRM SiaIyILewis Xmoditied x i V giycoprotcin gt Pseieclin GMFMO CDSA gtEselectin CAMI ELAMI I Activated Integrms I ADHESION Mucinlike glycoproteins Sialyl Lewis X P LI amp ESL I m i V ntegrms Selectins CA MS If h m Mediated by integrins ICAM1 and VCAMl 05Cu Lox 4 w N A40quot Eh at OICmA P j J 39 V005 sub 39 ujh bums VS insmoans vmeuMS r2 quotW VOAv climogl W m quotquot l gn W 030 lm0ugocnrl S but how ml as rue9ng Paracrines and Autocrines Long Distance Communication Hormones 39 Local communication Signal Chemicals I c Aulocn ne signals act on InI same cell that I 1 Hormones ave gemAer Cquot ew c n c I I 39 e Ma d sccr led them Paracrlnc Slgnals are only lard21 Lu lS win is quot1 r m g 1 t at g secrizled hyone cell anrl dillusetoadiacem V gt 7 V diffuse to target cells waive a go 77130quot r gt w 5 2 A Decanter i V r Example Cytoklnes v H Transported via aw receptor on i ll 3 5 blood 1 M v I i 39 2 same cell Receptors on target i u eighboring m P H cells Figure 63u long dimnmc cclltoccll coxmnunicalion Figure 610 Direct and local cclllo ocll wirummicnlion p vmvu 63h co are aquot iJ tUfcl 34 lial1L i0 03 imam nu39rvw l n li v39vynl Elwllguwn39dmnin in vLInquotrquotquotgt LJQm iw Orci Stawcl Vic NJ W351i l EiiC lefS AOHUthmQ it Woks ltirM 39Ut LLLOY g cm h uuf A mnu 01 L hammerg prLRmm Q cliqferee i mommm M PL iws on whitl1 quotr cg g mrs ilXs cavppz w 39 Timur 3 Long Distance Communication an Long Distance Communication Neurons and Neurohormones CODS MU Neurons and Neurohormones b Neurotransmitters are ereInseam secreted by neurons that adiosr 327055 a small gap to the target cal Neuron ose electrical Signals A 39 jiL39T FLi39sz39 39F il i VE U P W Electrical signal down axon Signal molecule neurotransmitter to target cell Hormone transported via blood to target Sfl ICLPH c 39 Mmlvavxgmi llef CutC Chri Hulajeel Figure 6 2b a Long distance ccllloccll communication L m m m1quotfigggjgn gz klnkgng distance cellloccll communication NJCLm lWrmoM VS humoM l l 1r lztx wwwcxrzmi Eixnlirr in withhm 1 nmmw39innv 7 4 12 395 L C mamae I quot39 CQWM P39 mmm KM at ha 5 3 bait 216 y r n H CMALUC lm a 393 fpfd SDLJOLQ w nuC fQu ffC jafbgw Signal Pathways Receptor locations Signal mmecurel Cytosollc or Nuclear mndsfo l gt Lipophilic ligand ece or enters CEquot Signal molecule ligand Rproltgin Receptor n Um vmzmb YCWLQ I Li I cylosal In nuceus molacu as i use through the cell membrane and Often activates gene Slower response biquott quot s quot 39 39 nuc ear receptors Intracellular signal VJWS L l39 g 39 Ce membrane I I 39 39 quot 39 39 39 I 1 U V r Target pretem L39POPh bC gand Wm rquot Targe wW on Surfaceofcellmembrane terns ml Outer surface receptor l Fast response Figure v4 39l argcl cell mccplm39s Figure 3 Signal pmhways Response lkrtlw S39tpchamm marshal on 7 Drown Membrane Receptor Classes Membrane Receptor Classes X b 39 39thracullula nal R ules I Ligand gated channel l 4 I I 1 r w I m 39 Receptor enzymes J OWM h mm W9 m 4 Gproteincoupled magma Integrin I a we x I I h engine prolexn V CXtoskelelon L3 vown MULCLHJ 1 L31 ml 39 7 quot Ll and blnuln ng3l0 l192quot9103 lt m 390 Cl WW Y S icjix almj WW CUP W R Q WWquot m w a 7 tuftQM 397 at p l vC M x r 4 leHrt l o LOMWMCHTO non Wow a Q 9cmch Signal Transduction Sl giial quot medulla Dinu I 0 V r l Membrane receptan l inmates 9 w Signal uamauclion W by proteins Transforms signal energy Protein kinase Activate proteins Phosporylation 7i Bind calcium mimmmcdw i Calaumgvall nc ngj Cell response e er 7 we teen respmso l E 1 l i 39 I i h ll H H M Figure 68 Biological signal transduction i u39i39 dig a w r m is I t l t HALll 3 39 Wenols an h fmgl wcl lls FCCW 3912 obey hoing n4 tom mU Ho LONquot Sh m Covwa Lox 339 Lot QLL Receptor Enzymes ECF Transduction Slitilr i39i i ll l Activation F 1 males Call p I c membrane 7 Tyrosine kinase on Side enzyme L 9EP39asmicsl l Active binding site A l Example A G Erodgpnhorylated ADP ICF Figure 610 Tyrosine kinase an cxamplc ul39a rcccplor alzymo insulin Wield h c Subunil nkl TLC C lhhlbihvk Sv bbl ll which bcl 0M 5 Cl anurbol39lt W TMOM Starts Pets 03lmcxlt3bnv Lambom WW ON Amplification enzyme Cascade Signal Amplification Receptor signal ligand complex activates an amplifier enzyme Extracellular uid Cell membrane Small signal produces large cell response Intracellular uid O Q l Nl 003 330300 m m KMlHl llll a cocoooooeoooooooao mm C a HULL 0 3922323333139123133 5maw Le P w auction l igun gt7 Signal umpli cuiion Cm lw i it J Bw s l 9 74 kquot quot lquot L j G Proteincoupled Receptors Hundreds of types Main signal transducers Activate enzymes Open ion channels Amplify adenyl cyclasecAMP Activates synthesis 1K hm Turnsgl l fund of NtL Mona Cramps imefhpruz 14611 H allot o S GProteincoupled Receptors Signal mlewla binds to G Wotem m o G proteinmated receptor counlod which activates mo G protein receptor 39 0 G protein Iurns on adenylyl cyclasa an ampxmer enzyme 0 Menylyl cyclae converts ATP to cyclic AMP Q CAMP activates proteln kinase A 9 Protein knase A phosphoryiales 39 Vulems leading unmater to a cellular responv so Phosphorth 069 630 00 protein I l V V V V V V O 000 000000 000 0 I 00000000 00 0000 00003000 I r a i I s a Call 1 I H H 39 l quot4 391 quot response V lt 7 y lt15 lt1 xi 00 00 DODQOO 60 DEC 30900 930 0 can 09 0 00 00 DO 000 00 a an 000 one no one woo no 300 0 no on no we on as coo no can no one 090 so can can no 000 39 ll The G proteincoule udcnyly cyclascCAMP system z lught314i39mr u FJJtrzlli39n I ull hmgm Mum 0 Protein OH ATP Protein O P O ADP 0 Pi H20 Protein Phosphatase 0 A 39 39 transfers the terminal phosphate of ATP to a hydroxyl group on a protein 0 A 39 catalyzes removal of the Pi by Many enzymes are regulated by covalent attachment of phosphate in ester linkage to the sidechain hydroxyl group of a particular amino acid residue serine threonine or tyrosine O Protein 0H ATP Protein O P O ADP if P H20 Protein Phosphatase Protein kinases and phosphatases are themselves regulated by complex signal cascades For example 0 Some protein kinases are activated by Ca c activated by Phosphodiesterase enzymes Adenylate Cyclase Adenylyl H H quot quotM catal ze Cyclase catalyzes CAMP NHZ y ATP 9 CAMP PPi N N CAMP H20 9 AMP gt The phosphodiesterase that Bindin of certain hormone g s K I cleaves cAMP is activated by eg epinephrine to the outer surface of a cell activates Adenylate Cyclase to form cAMP within the cell phosphorylation catalyzed by Protein Kinase A Thus CAMP stimulates its own degradation leading to rapid turnoff of a cAMP signal Cyclic AMP is thus considered to be a second messenger Most signal molecules targeted to a cell bind at the cell surface to receptors embedded in the plasma membrane The signal is usually passed om a 7helix receptor to an Only signal molecules able to cross intracellular G protein the plasma membrane e g steroid hormones interact with intracellular receptors 39 Sevenhelix receptors are thus called GPCR or G ProteinCoupled Receptors 0 Approx 800 different GPCRs are encoded in the human genome A large family of cell surface receptors have a common structural motif 7 transmembrane ahelices iL the rst of these to have its 7 helix structure con rmed by Xray crystallography Rhodopsin PDB was 04 Q 030me leucotc on L it ioQ Q J t o as Stimulatorv and Inhibitory G Proteins 0 G proteins are heterotrimeric with 3 subunits 05 6 7 Effects liomwne 39 Rs 7 Hormone Bi 9 A G protein that activates cyclic AMPformation within a cell is called a stimulatory Gprotein designated Gs mquot39 quotquot39quot quot quot quot P quotquot quot Inhibitory wguimivc 0 Protein Gi Stimuli wzth alpha subunit Gm my I llnhllm cyclm tlc39n39lyl 0 Gs ts activated e g by receptors for the hormones quotAquot y W m PM cycling u I I C 4 epinephrine and glucagon V l A Phosphodlnttrm The adrenergic receptor is the GPCR for rim W epinephrine NW fquot 3939 x u Cg Pm i lh 3th EL WE Wm Pm laxJ Lapping WW h rr fquot 39 39 A SW21 ormone 7 signal outside outside plasma plasma membrane membrane a cytosol i Cytosol ATP CAMP PPi GTP GDP ATP cAMPPP 3V The asubunit of a G protein Ga binds GT P amp can hydrolyze it to GDP P GTP GDP The sequence of events by which a hormone activates a amp ysubunits have covalently attached lipid anchors that CAMP signanng bind a Gprotein t0 the plasma membrane cytosolic surface 1 initially Gcc has bound GDP and a B amp 7 subunits r a transmembrane protein with are complexed togethen tosolic doma 39ns forming the catalytic site a 11 i GB the complex of B amp y subunits inhibits Ga t39ll39li gt39139v7i 1quot rlt39utr 7 zm E39Llllli39 ihn39u39 nquoturmmya 39wpu n1n QM WW isms WM H6 MU G F sMam We llmti c outside outside plasma membrane plasma membrane cytosol 1 cytosol GTP GDP ATP cAMP PPi 39 GTP GDP ATP CAMP PP 2 7 Ff I usually to an extracellular domain of a 7 helix receptor GPCR causes a conformational change in the receptor that is transmitted to a Gprotein on the cytosolic side 3 Substitution of GTP for GDP causes another 0 the membrane conformational change in Ga The nucleotidebinding site on G0L becomes more accessible to the cytosol where GTP gt GDP GaGTP dissociates from the inhibitory By complex amp can Ga re39eases GDP amp binds GTP GDILGTP exg hangg now bind to and activate Adenylate Cyclase q t mosaic th m u 509w 49an Lami 1 11 um 39 Agl WERE 5 G7 PAHin moped Louplefl q 00 J 5ampde N u a 39 H brm gm 39 65quot as 01 39 quot ak 9 Li 391 Shuln l e 06 a 7 signal outside u plasma quot W membrane I 1 Ga hydrolyzes GTP to GDP PM i cytoso The presence of GDP on G0 causes it to rebind to the inhibitory By complex GTP GDP ATP cAMPfPPi Adenylate Cyclase is no longer activated 4 Adenylate Cyclase activated by the stimulatory 2 Get GTP catalyzes synthesis of CAMP r 39 A CAMP AMP 5 tayze hydrolysis of 5 Protein Kinase A CAMP Dependent Protein Kinase catalyzes transfer of phosphate from ATP to serine or threonine residues of various cellular proteins altering their activity 39r il n h w H Am V Vquot V 39VAN39Wquot w r WORLDS consist 9 3 Separate 3k B7 in 3 Sbbun39ihs Summier d Scanner 1 v ltlt IK Kmx x
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