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2005,RRE/AB,SITH ITB
INTERAKSI ANTAR SEL-SEL DAN
LINGKUNGANNYA Biologi Sel basar BI-100A 2005,RRE/AB,SITH ITB INTERAKSI ANTAR SEL-SEL DAN LINGKUNGANNYA 1) Sel - Sel 1) Sel - Matriks ekstrasellar!"ari#$a#% 2005,RRE/AB,SITH ITB 2005,RRE/AB,SITH ITB - Basement membrane Basement membrane Dermis Specialized cellcell contact Specialized cell substratum contact Reticular fiber Proteoglyc an Collagen fiber Cell surface receptor (integnn) Fibroblast lastic fiber Dead cornified - cells pidermis Di!iding cells 7 -
Y " #traceld m Site ol Cell-cell contact $ctr%ablyi of eoirie &irmly 2005,RRE/AB,SITH ITB Cronge in cytog%le'(' org)anizalian C*ange ri riurneo*ilte +t%ation ',() syinttesi +li!abccol Ftf+l$ syn-ties-S ( ) 1 F i r e i f ) 09!ielami 11_ \ & A - 2005,RRE/AB,SITH ITB Figure 7.1 An overview of how cells are organized into tissues and how they interact with one another and with their extracellular environment. In this schematic diagram of a section through human skin, the cells of the epidermis are seen to adhere to one another y specialized contacts) !he asal layer of #tracollular matri# epidermal cells also adheres to an underlying, noncellular layer (t*e basement membrane)) .*e dermis consists largely of exescellular elements that interact with each other and with the surfaces of scattered cells. !he cells contain receptors that interact with extracellular materials) 2005,RRE/AB,SITH ITB Tl'a-(-)) *+))0E,L,- Ei ./ ' a I0 -)))1)2 # i/i-r Mel 'is2i/i 5 Er . .ar - 0/..i2# EI1M-I- pl -) INIMA*ELUILLIL RE*E3r0))Sla2 ,Ea, I la r Err2 )- 4i #' i #$ R .2' L-ca - i$#a )- 0r2/ ) i 0i '-s2l )1) E IR E rE 5.2ri 02r N6, /,r2i ' 7i, 2r # a #8-))9r5 E'- #a # 528r :/a I ; ar r#a 8 2 / ii 0- a#' # a k.l, <2r Ei ' ; )9 r/2# E I=EL L S LEREA*E >E*UT61)15 -))%))9)8518r ?2(,-? .ri B5 r r.' .; .r# k2l l@ *D a 5. # 2r .8s. B i rri. 10#al ,.ra.. I 8 'r, ,i/ l1D,- r.2 0el r27 i r/1.li/4 rl ( E i r.l i #er2;i 0ra ) LE- r. , 0E) r al 11s GI3 t2 )9 i #' 3 *- 0r... iiA *- 0r Di7 ii, Bi 'i a to chcd GM?, 'is. ;4 t2 tic Lr o ro 3; 5i5 ICD r@ i/i a#20 0raa' # Li# ir/ B5 ki '. ; E- r/2r/a, r2 ' ,Ha i # t; . rr.s *;.#i2ll@ 5rE' H ) ki 59 /- .rBi - ri .r# )1rA #. i2# . ;al #. )r 0r #i:i# Ea rr# i#Er 7 , # Eral 5ars 0L2a@/ i. r E , 0i7-ra S )-))9 I.-0/7 )(- r r#.r# kr 9#. 5r2tei# *-5r2..i#-li#k.' ti i/ #- FiC b ) MT, 13 - 3nc r27 5al rr 0ri1a'1I---i'D .5/5la#i. li#'liEEsi. Ear a 5ra/i# 3 MEI *AL .2 4rrAL-r 3i? DT)) * ELLS E;, .a / .ria I- *@/# 5l 7.r# i. .2 / ,i a r2 i.rB21# E#B il 9+)i # )9 i #$ 5; # .2' ) Bal I- ,))99 2' ) i# 9 '/, *2r# ri ri 2' ri$ F - rE '2# )1./21# 5l#r,))- Sorb= m3rlecr. 113h i jitti 113 ri3131irr9!rA 1 " rIrr i i or 31rmali#idr $ =11mcribralc %id& board' 1 = (" ro o)' li(ros "rad *de +,s -.rro.dscd1 I+ d #& ,h c all /r,& = s i s di co0 lidds =1- ,ir dic r al di di s , msc ri s I "m= =me b. , 2A bill i 3 the =IL 4o56 ma mci. I to- a=1 i . i7 0 (5 , o o) cro-d7 ((o i (o01 ,. . c18! a irig Aclmrig jorda0 9liime =1 . co"c d7r =113. chrom"h o)mrir5 Ad hc ro. i cr.di c. r %ra ro r0r 10r3c )i b ro La Aa #, ri s :di a0 9r acie #rarcir .= cra=1 1 .l a. m3cr i7 ,l 9 , 1=1=1 10101 ;a" j. ,,L (a S 7 ,rsi . m cr (rA c co m = a <4ro.rimig :,do0allo5. #r(is cr=sdrga ="i"e #.3 migc # rmal 1 ri lo5 1 = #rom 3I 7.r# Eel D/ 9 4 " E#'2kri # %i"e "e&am"aia mole(.l si&al (A) ENDOCRINE endocrine cell (C) NEURONAL .:13) PARACRINE 1 - j1 CONTACT-DEPENDENT body Crp r.r.#1 Sira. brr >-1 r & & 2 I 3 G 0 Im&-1- rl DI d!l "L# $ - ?r s e l t ar ge t j a.h @ hor mo diba5a melal.i "emb.l.h darah " 5arakri# 2ediator local -:mem"egar.hi sel target se(itar8 tetagga " dir.sa( oleh s.at. e-im e(strasel.lar ata. diimobilisasi oleh ,<2 " At2kri# / !.2#ta.t 'e5e#'e#t% sel res"osi) terhada" s.bstasi &ag dihasil(a oleh sel it. sediri ata. sel se(itar&a " Si#a5tik!#er2#al% Ae&am"aia si&al da"at dila(.(a dega cara "rotei dari s.at. sel beri(ata lags.g dega "rotei lai "ada sel lai. 2005,RRE/AB,SITH ITB r1.10 it#ir2A'rikl e# s#i# rgur ogr ona- SD/ 2l 5-D i7 3a7- a:-'s r;@ /i' $la#' ,C-r# I' '2; , 9) ;aa 2r E /i#s Eli '-i IBa <*- 2r '7- 7r#l#2 a.l' 5 r a / a# ' I 5l )1) traak'2B#- ' I # H-1+ a #' * 4 MU )9 I*E slars.- 5alkGr- 5 3DE-I r- .@# Ma. *-- a #-1) Il5l' #iI )s0 G--E-- I# 3AH 2Ais I#.l.i:- a#' /a I# #i#s- la.2#.lal@ /a Iii -//I ; sra. *-) l. ,li MU )9 I*IS 0N- )9 Ism 0 I 3 - 1!)1 & r. I i@5as d al - 3eal13ea- 2r r;2II#a $JM3 2r el-1- a/ I #2 a. I' $l:r#k a'' E-1.la/5/ ri.-0 1 ) 0@ ra#sr#; 7 /a#@ ri' @a- /s. E$2 ra# arr1I I# 2A-#i#l ra#.ts K/ G I.e% , #2Kr2;arrs/l L KI )99)0 9) rid C.L+ s-rKa7# G-Ar# +(1e.eiF. l. a .it? ri(A-L-2)% #- -ras / #a I s #Gl@a i:irri#als *2 #t-7)-+)+)0-k #'+.' )%-0-9 )5 #aIrE H2l+k LI K*- 5i.e51.il@a raKr2rel Birl2as 2'Bi 'a@G+20+#e 25II r@5t #ai$;t2rI#$. al4 r#%/ I7-.2/i#$ s5a.;ita7l I# E-a#7i Ba@ ae- '7- Marla I#$ rrare/--/4 ri#e 5kaDl# %ab I e 1;-1 S7# e r# 5 ks 20 i$# el I I el SI ;hl 1@ L,; LL E SI%, # <1 , #1< #.L .%LD, S/ , A<% 10 ES Hrtrr2rss 9GKINI al ,I a#' '5i l@arl@-52r '7- 7r#l#2 a.i' l@k. I#. /i7-)AE- ti.2' 5asi/1In Mar. ra/, a#' /.i#t2lt/ *2e re21 a.I#ai al 0 ari' E-EE2l' i'a+ 3ea i 3ai 2r ;2lirsEl I al3a..- /a-.4t2l ti# 2r 5i..ire-- .ait3%;@.lrari.-- a#.l li5i's I# /.e: ':-.e- E s 0Y9 @ E-E-r2 i'all@all@a 2r . ;2la 31+ I #.l. +.- 9 #' M9 h d #s- -sa.2#.la rE Al S<FL,I I *itM 422# %c 2Ai 5a#e r@a s 5A5il'.G 2I i SILF .0 ) 1;. 11 10-11' Al&</,01 I4I</I<<#YA%I Ir ---HI% /aB .a+ti 'te-23ail $as ..1F- 111111 - G 4l22' C-0-'s E-r) MU la )-95 Idair I a#' /a#@ .elia. *A I - Bas .i 5 51+)IAEa E-r) MU )9 )-95 /a#@ 21-) raCe# i2 55 1+ IEera "r/I%1010$$. ,- ) .1 I tit Sad << .a#al?% LI2e:+:- al raKr2rei 5 /.sas sBeat? 2r r;a+i s7)1+ - )E- I#;I4la .al K2#a-H2#15 I2A2S gamaal.lmr /a;l7 5ir.l.l2# .asas @$re-als ra 'lae a#' 4a.2/a- kaki- ;a-5i#$ is I#la/ /ai/ .ases s#7i/; /ir/ la Das i2 ra471 /i'is1al raBar'@lr@ @a i )1NKr- c. Is I t:-L5as 5l2ral# 5keii# d aitea'Ca- 2r '7- a/i#2 a. ;til'lra r2ta rri I I ars 1 Sel 4erk2/#ikasi se.ara ki#liaBi 1 Si$#al-Rese5t2r M2lekl si#@al 4ekerFa 'e#$a# k2#se#trasi re#'a; M)0-OM < rese5t2r 4erikata# 'e#$a# aEi#itas @a#$ ti#$$i, /e#i/4lka# sat kaska'e si#@al i#trasellar @a#$ 'a5at /e#$4a; res52#s sel- M2lekl si#@al 1 " 5r2tei#, 5e5ti'a ke.il, asa/ a/i#2, " #kle2ti'a, " ster2i', reti#2i', 'eriCat asa/ le/ak- " Gas terlart se5erti N6 'a# CO Ke4a#@aka# /2lekl si#@al 'ikelarka# 2le; sel 'e#$a# .ara 1 " eks2sit2sis " 'iEsi !sekres6/elali /e/4ra# 5las/a, " terikat 5a'a 5er/kaa# sel 5e/4eri si$#al *2#t2; 1 Pia$ra /era#$sa#$ 'isekresika##@a $as N6 s;$ 5e/4-'ara; rela7 //ele4ar 2005,RRE/AB,SITH ITB *2l 2' ` Ho r mo n e !a% -ntracellular receptors Carrier protein in blood A Cytosolic receptor Receptor-*ormone comple# 3 u c l e u s 1@0 Cird lo "ra5 SIIIHI%1 E.9<l! I!LL Mrt- 1I $ltered transcription of specific genes Er nRNA r el k" " L A W t i I I ri$re i-iC 3I HIM **M LAHA ))))5)r M*PII) MIMI* )))10)1))>)) 0l MIL al Di#i#$ -) - a E47) Cessel- ))1)I SQ-/re Ire's leaEi#$ 4 !))81+ - ) .G t;e El22' @e 1A- iekase' 4@ NerCe kErri#1- i# t;e ;i7'AterB1el 1Ai'< e#tke5eli .elk ) - t /ake a#' rekase M6- iit- 'iEEse 2E t;e er'2t;el;la#' iita Mi:e 1/at; Y"IKI rhroi E5i#eEri# 4erikata# 'e#$a# Rese5t2r terikat 5r2tei# G HOCH% 4 &O ' (P &O I O& D ' UDP-)l*co#e " e5i#eEri#4erikata# ke rese5t2r 4-a're#er$ik 5a'a 5er/kaa# 5lycogen synt*ase HOCH% &OCR% -a- '''\L/ H OH 5lycogen (n 4 ' residues6 5lycogen p*osp*orylase HOCH, &OC&+ - D " O& sel ;ati 'a# a'i52sa- m ' '( P(c ( (pridine I m ' UDP " E5i#eEri# @a#$ 4erikata# 'e#$a# rese5t2r /e#i/4lka# eEek 4er4e'a 1 &OC &, - ( OI .L$O(LO &O O& ( /l*co#e 1-01o#01!%e ' ( 3 E - $ $ ( ! O& OH 5lycogen (n residues) & E5i#eEri# @a#$ 4erikata# 'e#$a# 4-a're#er$ik 5a'a sel 2t2t Fa#t#$ + 5e#i#$kata# k2#traksi 2t2t + s55l@ 'ara; /e#i#$kat 2005,RRE/AB,SITH ITB & 3a'a sel 2t2t 52l2s i#testi# + relaksasi 2t2t & 3a'a sel 2t2t 52l2s salra# 'ara; 'i $i#Fal, klit, i#testi#+ rese5t2r lai# re.e5t2r a2-a're#er$ik + arteri k2#striksi Protein Reseptor : cl 076,1, !(/ C) Edracobrir 2005,RRE/AB,SITH ITB ti 1 - 1 1 11.0111171 1 11 el PIPI - P!I"I#IIII )))TRA *E L L * * 0rT6re r 3 I h - tea "hctic R# r o 161$$I ma r3 I ri l. lar rci) R$ire )E-L E7tra.elllar #i$#al r#2le.-lt 4i#' eit;er t2 .ell-- - ,riare re.e5t2rs )1. I% int /< 'llar era1a#t-) 2r re.e5t2rs- ),)) M2sI Ei$#a r#ale.le# are 4il$e a#' ;@'r25;ik a#' are t;erek.e tread F7 <,ISS I;e 5las/a /e/4ra#e ';e.ilA i - Istead, t;e@ ;i-' to cel&s'iace rere5t2i#, B;k; 0- ILr# $e#elak 2#e 2r r#2ieli$#al#i##i'e I ;e ta/eI .el *ars 2005,RRE/AB,SITH ITB ;2B# i# 0i$r- 98-()- IR- 52+#e E/ail I @'r25;24i. #i$#al r#2leBles, ;@ 'iHse a.res-s t;e iar$et.eIrs5l-B/a 2IH-3 #le a #' !1< I era@/es 2r ;il' i#ira.elllar #7e5t2rs--eii;er rr i;e .@ke,2) -s;2B#% 2r i# i;e #.leE- #I;J,L,7! <rl .ri-s. ra-m"Lor) rocoroi7+ ool&.r"oiric moloc.l@..Sigalmolcr.(s 5ill hid a I# ra ch Lac is I i "l 3..i o rsrc" ro- r # i ro 5ish a sh3ric i)o r.hi ih'7 co' 11 r is BI%. A-3a'a /e/4ra# sel 1 /2l lart air i-e- #er2tra#s/iter < ;2r/2# 5e5ti'a,Gr20 B-4ala/ sel 1 Si#@al ;2r/2# @a#$ lart le/ak !ster2i' s5t estr2$e#, 5r2$ester2#, test2ster2#%, asa/ reti#2at,Pit 4, $as N6 )%'ala/ sit25las/a 2%'ala/ i#ti sel 2005,RRE/AB,SITH ITB 2005,RRE/AB,SITH ITB AktiCasi Rese5t2r 5a'a 5er/kaa# sel + kel2/52k rese5t2r 1 1. Rese5t2r terikat 5r2tei# 6 (> )00% Li$a#' - rese5t2r + aktiEasi 5r2tei# 6 + aktiCasi/;a/4at sat e#:i/ + /e#$aktiCasi i2# .;a##el ata se.2#' /esse#$er- *2#t2; 1 rese5t2r #tk e5i#eEri# !B-a're#er$i.%, ser2t2#i#, $lka$2# %. rese5t2r ion channel Li$a#' - rese5t2r + 5er4a;a# k2#E2r/asi rese5t2r + alira# i2# terte#t !K,Na,*a,*I+ 4a; 52te#sial elektris 5a'a /e/4ra# sel- e$ rese5t2r asetilk2li# '. rese5t2r @a#$ 4erikata# 'e#$a# tir2si# ki#ase Rese5t2r ti'ak /e/iliki aktiCitas katalitik- Li$a#' - rese5t2r + sti/lasi 'i/erisasi rese5t2r + i#teraksi 'e#$a# 5r2tei# tir2si# ki#ase 5a'a sit2s2l- *2#t2; 1 Eakt2r t/4; (. Rese5t2r @a#$ /e/iliki aktiCitas e#:i/atik i#tri#sik Rese5t2r /e/iliki aktiCitas katalitik i#tri#sik- Li$a#' - rese5t2r + katalisasi GT3 + .GM3 ata 4er5era# se4a$ai 5r2tei# E2sEatase + /e#$katalisasi 5ele5asa# E2sEat 'ari 'ari E2sE2tir2si# !rese5t2r tiEt'i0iEkiii<M%- )-) 82#t2; 1 rese5t2r i#sli# 3e#@a/5aia# si#@al/i#E2r/asi ke 'ala/ sel 8.R$C99:-$R C-53$9ry';9C:9 RECEPTOR PROTEIN I3.R$C99:93R C-53$9-35 PRC.- TAR/ET PROTEIN2 me tal#ligene regulatory cytos+ele enzyme protein protein altered metabolism s*ared gene e3pressio n altered cell s*ape or /?Ate/ant Si#@al 'isa/5aika# ke sel tar$et /elali /2lekl i#trasel 'al - a/ " I #isiasi & Si#@al 4erikata# 'e#$a# rese5t2r /li$a# 1 RE#:@/e-li#ke'R < 3r2tei# G & Si#@al+ li$a#' 5 tra#sE2r/asi si#@al ke /2rekl lai# 1Rse.2#' /esse#$erR1 *-AM3 < *al.i/ " A/5liEikasi & A/5liEikasi si#@al @a#$ 'iteri/a1R.as.a'esR5r2tei# ki#ase & 4istri4si si#@al #tk 5e#$ar;i 4e4era5a eEek se.ara 5aralel 2005,RRE/AB,SITH ITB i d EA Lod cc am 10@ai ci ; r. " r=1 A GGN.li "Qe EI g 3 I r-0- .l 3 =e a-al AFK. ?I L3 I #,L "h -0- "h 10@ - 1'@ 3 (m',1 " r.3 riM. I1-3 r& #rei ro"-I mr.3 #r- i %I/ E 4 E L F J Talk 16-4 Sa#t Res52r'es 3ik'i$ik' 4 - % 3l - /5;2li5irse * A.iiiratki# H6LE*ULE PD1B;i# la r2; trr2756 k$i@ktritK- TARaET TISSUE Il@aI " 3rN0 )))-+DR RE36NSE ElEi# # Ma2 i.keer # k$@kkit$- %h,iti - 02l'@ lc in:yrroa Ba'i rr# i7.l # is. re )G-2+ A ri<e i# i#traGlllar 2EEi.lk - )5) ) ))))1? .-a# $rit tr2#-s.ri5li2#- ) i/i#iS 2E a I#K-I/2#e #ets /il ler l2 ie.e5l2r .a# lea' t2 i ;e 2E a.le# @l .@.laSe a#' a " i#tra.elllar .@.li. Mel0I I# t;e .@l..-1-I- .@.li. >-0-) 9 !1< I iBate - 3 M-A- B;i.; I;e# rrr12re 3 i#k t;e #.le--s a#' 5;.rs5;2r@ later s5e.ilk #eG re$lat2r@ 55atei#s-- 6#.e I#..-5;2r@ la le'- t;ese- 5.2lei#t - - sti/la I*ee tra#s.ri5ti2# al a - sei l st-re-r-- T;is l@5e- 20 A$#ai#$ 5at;Ba@ .2#tr2ls /a#@ 5/-.e-r:-e-s ra#si#1$ 1011 - 1 0I.i/2#e E@#t;esitT i# e#'2.ri#e- .ells l.- t;e 551'.li2# 20 irrr2l TRe' i# lG#s-teir# /e/2r@ I#e A.lirate' " .a# -als2 5I#..-5l - r1.@ la le a#' I;ere4@ le$la le- 2l ;er 5 - 2tei#t - - a#' era @##es " l ;e .@l ..A $1a- s i #'i .al e.l 4@ t;e )? - e- r "able 16&( 7#t H2r/2#t-i#'.t' it I>t 11N YA1 Mt'ia4t' ) !*clic AMP , FI>di<, L LLIA > SI GN AL 1.1 0 LE* LL , I --' 5/ II#.- --' Ao 3IIc. A' 5# 31 kB, A*T H, -, LF a t 1+) A*TH I# . /2s1- I# ;e# # #' I a# r7'a# <a$2 I/2k-I7er# L6 I Ii (dm .2r I s2l r2/a# t5" ;2$; a I Dr re 'iCa I /a IEr#i 5s- Is al I - $1 4IL he.111102 ,<II%$= imsgs ,4 (m 1!00@1* 4rri la l?AI3IrilE#kRIS a )L atiN /ai ' t& c&cl ( AN01 Respon sel terhadap sinyal +elen, ar l'da- .Lot 1 /L'n0 +ontnai ABotilkolin I I ,ccoC11,CHNIC1-1, Peattransn -ecepatan dan It1ntra-si otot 0 ! 2 s p D p t o t i c cel I A. ) si#@al + ) ti5e rese5t2r a#eka eEek 5a'a 4er4a$ai sel 4e#tk sel, 5er$eraka#, /eta42lis/e, eks5resi $e# ). Setia5 sel 5#@a 4era#eka ra$a/ rese5t2r s5esiEik #tk a#eka si#@al sel /e/4eri res52# + /isalka# eEek #tk kellsa# ;i'5 < 'iEere#siasi 2005,RRE/AB,SITH ITB La#$ka; - la#$ka; k2/#ikasi " Si#tesa /2lekl si#@al 2le; sel @a#$ /e/4eri si#@al " 3ele5asa# /2lekl si#@al 2le; sel @a#$ /e/4eri si#@al " Tra#s52r si#@al 2le; sel tar$et " 3e#Likata# si#@al 2le; rese5t2r s5esiEik @a#$ /e#@e4a4ka# aktiCasi rese5t2r terse4t " I#isiasi sat ata le4i; Falr tra#s'ksi si#@al i#trasel " 3er4a;a# s5esiEik E#$si, /eta42lis/e, ata 5erke/4a#$a# sel " 3e/4a#$a# si#@al @a#$ /e#$ak;iri res52# sel 2005,RRE/AB,SITH ITB KK,,&-K&KKKK----- t ---------&,? *ELL 0 ) TARGET ( Re.e5t2r 5r2tei# *elllar res52#se1 a.tiCati2# 2E a $e#e a#' s@#t;esis 2E #eB 5r2tei# NeB 5r2tei# S t e r o i d hormoe ANIMASI 1 " Ster2i' ;2r/2#es 4i#' t2 i#tra.elllar re.e5t2rs - T;e ster2i'-re.e5t2r .2/5le7 4i#'s t2 DNA, tr#i#$ s5e.iEi. $e#es 2# 2r 2EE !re.e5t2r a.t as $e#e re$lat2r% I# t;is e7a/5le, a #eB " 6t;er1 a.t as E#:@/es, e$-N6- $a#@l@l .@.lase-.atal@:e s@#t;esis- 2E GM3 2005,RRE/AB,SITH ITB 5r2tei# is s@#t;esi:e' +1) A ;2r/2#e 4i#'s t2 a re.e5t2r 5r2tei# i# t;e 5las/a /e/4ra#e +1) T;e re.e5t2r 5r2tei# a.tiCates a si$#s I H2r/2#e !e5i#e5;ri#e% RE*E3T6R 3R6TEIN I ---------- 3las/a /e/4ra#e %A>;,% <,LL tra#s'.ti2# 5at;Ba@ i# t;e .ell +1) A series 2E rela@ /2le.les tra#s/its t;e si$#al t2 a 5r2tei# t;at .arries 2t t;e .ell?s ornra/s *&i 7rla I '.<@1=.@iis@@.i@@@9br 52r,Ke@ ObN " trABe '' ' Ad cic9 < PSigal ad @.<JIQ I <.01 AI2: C@"H A3A=/ ) -K #tr010$1 "a5 < 1.- , roltr <R 10 0 -7 - @11 ! $ -' ) 1 - 8L 3Il L 5) ? @ .&&& 4 )'7i. 'i 9 ++TMI-II I --G,-K 5 1 i6 . 7l . LI I ?) ")tda -..... 1-- h&lol ) Iis"(e'"h al @. 1.d @@$ lit <@1 -? r$ii t@ a/- L , - Rela@ /2le.les *elllar res52#se !i# t;is e7a/5le, $l@.2$e# 4reak'2B#% Si$#al - tra#s'.ti2# 5at;Ba@ na'n aLmagirm rcrcror Lialm )99 a migal 9#$l- ih3moh 9 <."rarri' mBrrBchcmchrits.bomdcB&mc. da.l&d@claL%hiarmtiico&.?ti-achcrir, ii.o) r ti1A'5h()r (i+ aothe cola chc .0S1$$r i=LL0%h *lb0$m "0,lm3&. A cor3...clImbr rci="i7) ,(a c 3d. 3.7hcr < ra(loc..1cro&ic "hom"hdi"ac <. 2il cr&c-ciiiisci. i(F "mgl.ccic. irmic.1 =did9 lielo *6 9#el or ro cold.oi .A11111I11 i ihr miri(.rar, cl., e("lmiir roir.hm. *9 d)r ...lio Se#@aBa @a#$ 4erikata# 'e#$a# rese5t2r /e/4ra# - #er2tra#s/itters @a#$ 4ersiEat i#'ktiE 1 a.et@l.;2li#e, $lta/ate, ser2t2#i#- -- I#;i4it2r@ #er2tra#s/itters1 GABA, $l@.i#e & 64at1 Pali/ a#' 3r2:a. /e/5e#$ar;i leCels ata se#sitiCitas #er2tra#s/itter & Ner2t27i#s, s#ake Ce#2/s, .rare, a#' str@.;#i#e 'a5at /e/ 4l2k si$#al #er2tra#s/itter %able 1$-! S2/e S4sta#.es T;at Mi/i. Natral Si$#al M2le.les =- =-C S-53$9 =;9C:9 RCP.;R $C.-;3 FFC. >alium and barbiturates y-aminobutyric acid (5$B$)stimulate 5$B$-acti!ated relief of an#iety? sedation ion-c*annellin+ed receptors acetylc*oline stimulates acetylc*oline-acti!ated ion-c*annellin+ed receptors endorp*ins and en+ep*alinsstimulate 5-proteinlin+ed opiate receptors acetylc*oline in*ibits acetylc*oline-acti!ated ion-c*annellin+ed receptors glycine bloc+s glycine-acti!ated ion-c*annellin+ed receptors 3icotine =orp*ine and *eroin Curare Stryc*nine constriction of blood !essels? ele!ation of blood pressure analgesia (relief of pain)? eup*oria bloc+age of neuromuscular transmission0 resulting in paralysis seizures and muscle spasm I 2005,RRE/AB,SITH IT! <ell s.r)ace "roteis mediate cell-cell iteractios. " *ell 5 "ari#$a# 1 /isal 'ara; 'a# 2t2t Eor*& call coacoln8 a "5ciin arr*o1rArle9 r pro'ia. on i.-3 :'r-oc "liaa a r-an id9aci7*9scli r*p9 cacti; is a &s 7 p r9 t<a = >*. #I<J>,7.1@ ir .m' ri o) d. im.i7tlob.lio #.0Lil& oicill i.r)(0a s.r(ir #ai. % 3r,l , all r.s#ica (i" richrt chs irrr.rc ra"m, i or,"rirra b& sM3/i!mi (idriBE (aig oil rrcr(a- 2,, EI ciBcm 13171 all- 30c =Fl).= m ch- clic imic #licr 3 2IAS aI# irrradigcrtib' l.ch ,. I7ri73ii rimQ rd ilall&sis Lim all o) Irri%hrial arBril! 2005,RRE/AB,SITH IT! " Tia5 sel /e/iliki /2lekl /arker 1 /e#e#tka# i'e#titas R.ell-tisse s5e.iEi.R, se;i#$$a sel lai# @a#$ k2#tak 'a5at /e#$e#ali /arker terse4t- " Ma.a/ /arker 1 1. Glik2li5i' 1 // 5a'a 5er/kaa# sel, /is1 $2l-'ara; %. 3r2tei# RMaF2r;ist2.2/5ati4ilit@ .2/5le7R!MH*% #tk /e/4e'aka# RselER 'e#$a# R#2#-selER,e$- i/#2$l24li# A';esi a#tar sel 5a'a Fari#$a# 'a# /atrik 1 R*ell "#.ti2#R Ti$a kel2/52k cell junction: 1. occluding junctions: i-e- tight junctions + ;a#@a Certe4rate %. anchoring junctions A - 4erikata# 'e#$a# Eila/i# akti# i. sel-sel - (mis. Adhesion belts) i. sel-E*M - !/is- focal contacts) 0E*LIELE(- L. 2005,RRE/AB,SITH ITB%i clia 9 , #a." o) rill j.ccior. %ha chrcc it-ichrc"rBsi ..irrcc chi(i,i a hBo. a l.c.r o) the c,rcc m(t i!."ci. a) rdl j.a(ro. laciicsc ch/r ).aim0 OrN /BI* acbQ O$N 3ch.rig j.scioQ $.N r"rimmicio j.ccia. B. -4erikata# 'e#$a# Eila/e# i#ter/e'iat i. sel-sel !'es/2s2/% i. sel-/atriks !;e/i'es/2s2/% 3. Communicating junction a. a! junctions . Chemical s"na!ses a. 3las/2'es/ata !5a'a t/4;a#% LT5ii# lowialAitliiliit,. 0)) " a ;ti/ilkiar Tra/ - A#al1+/A 3rt#a'al + +)) A/i#2I kikti$ 5r2k're- k- 3I= #a M** Ma$#a rBrit.ri 8 i4%Ar/;2rti Ell LEK I !a% G..rtrikalti$ is i #2 li'l2 # Ti$;t F#.ti2#s 1 /e#$;4#$ka# /4r 5las/a sel @$ 4erse4ela;a# 1. 4arier selektiE 5er/ea4ilitas1/e/5erta;a#ka# 5er4e'aa# k2/52sisi .aira# 5a'a sisi sel @a#$ 4er4e'a 1. tra#s/e/4ra# 5r2tei# 1 .la'i# < 2.l'i# %. E#$si 1 -Me# Fa$s k2/52sisi se#@- 'l/ r2#$$a salra# / l/e# -Tra#s52rt #trisi se.ara selektiE Ti$;t F#.ti2# a#tara sel e5itel 4er5era# #tk /e#.e$a; 'iEsi 1 )- 4arrier #tk 'iEsi 5r2tei# /e/4r a#tara '2/ai# a5i.al 'a# /e/4ra# 4as2lateral B9 ;;D 2- /e#.e$a; ke42.2ra# 3-) /2lekl lart air tig*t @ unc t i on pl as ma membranes of ad@acent cells i nt er cel l ul ar space passi!e2glucose carrie protein basoleteral sur f ace 9;& 9;& 2005,RRE/AB,SITH ITB 7i0're 1?&( "<e role o: ti0<t ,'nctions in transcell'lar transport. !ransport proteins are confined to different regions of t<e plasma memrane in epithelial cells of the small intestine. !his segregation permits a vectorial transfer of nutrients across the epithelial sheet from the gut lumen to the lood. In the example shown, glucose is actively transported into the cell y ,a-& driven glucose symports at the apical surface, and it diffuses out of the cell y facilitated diffusion mediated y glucose carriers in the asolateral memrane. !ight .unctions are thought to confine the transport proteins to their appropriate memrane domains y acting as diffusion arriers within the lipid ilayer of the plasma memrane/ these .unctions also lock the ackflow of glucose from the asal side of the epithelium into the gut B9 ;;D A#.;2ri#$ F#.ti2#s 1 1. 4a#@ak 5a'a sel @a#$ /e#'a5atka# stress /eka#ik ie-klit/2t2t %. /e#$;4#$ka# sit2skelet sel 'e#$a# sel lai# ata 'e#$a# E*M A'a 9 Fe#is 1 1. A';ere#s F#.ti2#s + 0ila/e# akti# %. 4es/2s2/ + Eila/e# i#ter/e'iate '. He/i'es/2s2/ c yt os + el et al f i l ament s a n c * o r i n g @ u n c t i o n s e#tracellular matri# 7i0're 1?&6 Anc<orin0 ,'nctions in an epit<elial tiss'e. 0ighly schematized drawing of how such .unctions .oin cytoskeletal filaments from cell to cell and from cell to extracellular matrix. 2005,RRE/AB,SITH IT! actin filaments inside micro!illus micro!illi e#tending from apical surface tig*t @unction bundl e of actin filaments lateral plasma membranes of ad@acent epit*elial cells 7i0're 11&2 Ad<esion belts bet=een epit<elial cells in t<e sall intestine. !his eltlike anchoring .unction encircles each of the interacting cells. Its most ovious feature is a contractile undle of actin filaments running along the cytoplasmic surface of the .unctional plasma memrane. !he actin filaments are .oined from cell to cell y transmemrane linker proteins +cadherins), whose extracellular domain hinds to the extracellular domain of an identical cadherin molecule on the ad.acent cell +see *igure 11&7). Figure A0'Aburst Bd*ulioniarelitem%*e3cel+adlie3to li+ilim+grai9lib)'( !eil *3S liecii rtaiuod %is* iluureoeentatib.diamre!eal-l''('2C(i- ) '+ =ill li'S''')itrr2y)grtcn) and dic integnm (real).*e 9uepiniareb Plized in small pig*en (*it %topundlu t*e ritc 0 of roalli0 *erionni (*D.*ecyroplarmicsurlacemylined2betion+ieoli%d op*ibim crll isdro%n *ere *ri*e innereinfraell t*e membrane %ir rinirpida"ninen0deinp)eniinely r +) bundles of nibsolibinaema are gen ronaaarinietei+ i+ innersurfaceof=emeni*meint*eregienn@a S%at inbin+r (al Salicimilindra%imr of thigIldhsio $niE '')e limric) (o* ofirogriPgl!*ora%-tlful*rrprotciornnbot*-dern t*e lipid biluyer0 .*e binding of mmelbdui boli+ yell ;3F-- $lld itrunectin0 is l*oug*r indua c*anges bi t*e ryillaninie C-=-3-='D of t*e in+grin t*at egg) t*e inregrinr to become lin+ed rri pplig FC'''=* orr*cey) *E 0 bdrob) 9in+ages %it* -lic 0 )))ycoli+ele+on lead0 ?-- 3=-0 D lb lt*Rling ''''''2't'' =$- 9inbagrr %it* t*ery tus+eleton arc rn eclided by Gariaila daCn *buf E+ ro+ba)0(' as olio and a0laioin0tbalbind in -li b ednnlildl*rlmrp= .*e eytor <amnia domain0 ntegrinsarea*uass+<ialed%l* ed F$ :i!alioi+inau1)<-<*eat ).*e rac*irenronr*e inre$rin -n yn t3ifoolbild bgaud can dicit pmtcin + oases and start o c*in rpo rant t*at tannin gignolo '''2)2'2?ct''0 HPia -=$= -==''''((2 C--S IS-) di0=*y 'JJA?sK''(=S)"(''<')')DL =-''2'''' III%- tlI )ht'?.<> 18101..11!0@)li' iii'iQEAAILIIIII - 1010115 ''')RuKunlit lbirtssit tenet0)) A';ere#s F#.ti2#s a';ere#s F#.ti2#s sel/ sel 1 a';esi2# 4elt/:2#la a';ere#s - 'ekat F#$ a5eks sel, 'i 4aBa; tight junctions# 0ila/e# 1 akti# - 5r2tei# 5e#$ikat tra#s /e/4ra# 1 .a';eri#+/2l- a';esi 4er$a#t#$ Ca$% : gen "g /e#$atr R#asi4R sel - 5r2tei# 5elekata# i#tra.elllar1 .ate#i#, Ci#.li#, a- a.ti#i#, 5lat2$l24i# Cy'(J(' iransmilied 'n -l+ nunieuri distributionofdesmosomrsand*em-desmounues-n i*eltra*llrilint) he +eratin ;larnrnl --C-&;r+i of ildireerb contreered rra one anol*cr*roug* dinrnsisurrinS rains ititini/b +Aunud!snifi3dneS) MAI a';ere#s F#.ti2#s sel / /atriks1 02.al .2#ta.ts/a';esi2# 5laQes - 5r2tei# 5e#$ikat tra#s /e/4r1 i#te$ri#!U20% - 5r2tei# 5elekata# i#trasellar1 tali#,a-a.ti#i#, Ci#.li# - 0ila/e# 1 akti# 2005,RRE/AB,SITH ITB PlaEue containing protein plectin Cytoplasm Plasma membrane BP'M; -ntermediate filaments space N'' I34511(1'':6111.111)11.111+178 #tracellular$9->$ 9AN7:61+-) '(' Basement membrane $nc*oring filament (9aminin-F) Collagen fibers b) .ype >-- Collagen fibrils #ig.re 7.1@ Aeidesosoes are differentiated sites at the asal surfaces of epithelial cells where the cells are attached to the underlying asement memrane. (a) 3lectron micrograph of several hemidesmosomes showing the dense pla4ue on the inner surface of the plasma memrane and the intermediate filaments pro.ecting into the cytoplasm. (b) 5chematic diagram showing the ma.or components of a hemidesmosome connecting the epidermis to the underlying dermis. !he ot,p, integrin molecules of the epidermal cells are linked to cytoplasmic intermediate filaments y a protein called plectin that is present in the dark&staining pla4ue and to the asement memrane y anchoring filaments of a particular type of laminin. A second transmemrane protein +26127) is also present in hemidesmosomes. !he collagen fiers arc part of the underlying dermis. +A# *89: ;9<=>A5 3. ?3>>@, A. B3>> )I9>. %2#C1, 11DD/ )@ B96@8I=0! n-9=1SS-;3 9* !03 89B?3*3>>38 <,IE385I!@ 68355.) 4es/2s2/ ;e/i'es/2s2/1 /e#arik 'a# /e#$ikat sa#$at kat 5e#@e4ara# teka#a# /elali e5itel ke E*M 'i 4aBa;#@a 2-4es/2s2r#1 sel - sel , & a#.;2ri#$ sites #tk Eila/e# i#ter/e'iate & tra#s /e/4r li#ker 5r2tei#1 .a';eri# 9-He/i'es/2s2r#1sel- E*M & 0ila/e# i#ter/e'iate 1 kerati# & Tra#s/e/4ra# 5r2tei# 1 i#te$ri# 2005,RRE/AB,SITH ITB itar - a G 0 I G U R E 2 2 - O S t r . t r e 2 E $ a 5 F # . t i 2 # s - ( a ) - n t * i s m o d e l ) a gap @unction is a cluster of channels etween t%o plasma membranes t*at are separated by a gap of about ,-O nm) (b) B 2 t ; m e m b r a n e s c o n t a i n c o n n e # i o n n e r n i c * a n n e l s 0 c y l i n d e r s o f si# dumbbell-s*aped conne#in subunits) +c1 ac* conne#in s4#it has four transroembrane ay- *elices .%o conne#ons @oin in t*e gap bet%een t*e cells to form a gap-@unction c*annel) ')F,)( nm in diameter) t*at connects t*e cytoplasm of t*e t%o cells) eb: 0 i $ r 7 . ( . ! h e > a c a l i z a t i c n i o f e a t l ; e i r i # s i # s y n a l p r i c . i a t i c t & i tts& +ea) ; ne tech n#..gtie to localize a protein thin a seheel1>lar region is to incuate tissue sections %it* labeled an ri*ndies Fprepared aGgair & i,t that proteinG In this electron rraicr & o?&rap3t. a section through a s & saapse in a mouse rain has een incuated antiodies Bhlack grains) a h,ar ind ro a praecadherin. !he protocadhe ri>ocali,ed within the central re& gion of the si.tiaptie ?inction. +A) GA. model ofa syriapific in & whack&, classical cadherifly&hic- contain five extracellnlat &mains) are situated at the edges of the s. & napse where they & are tlaouerht to pro&..ide adhesion herween the nne&& and po.ts1tiapDr. memranesG 6rotric ad en +&which contain six eiciracellulae mains) are present in the center of the synapse chew are 3l & ,onni & it to nne&&diate speeifielev & in the interaction etween the rwo rare EI<IL,<<7'31 r - rr r )() - 7. )lit rB - r' )) - 7 ) *2//#i.ati#$ "#.ti2#s 1 k2/#ikasi sit25las/a Ia#$s#$ '$# sel sek Ga5 F#.ti2#s 1 a#tara sel-sel - tra#s/e/4ra# 5r2tei#1 .2##e72#+t'r atas 8 .2##e7i# - 'a5at 'ilali 2le; i2# a#2r$a#ik 'a# /2lekl lart air M )000 4a, /is-$la se'er;a#a, as a/i#2 - /e#@a/5aika# si#@al elektris 'a# ki/iaBi 1 /is kersaka# sel < si#a5s 3' t/4;a# 1 5las/2'es/ata S@#a5ti. F#.ti2# - sel saraE - 'i5era#tarai 2le; 5r2t2.a';eri# 2005,RRE/AB,SITH ITB S//ar@ 1 "#.ti2# eit #2# F#.ti2# 7 i 0 l i r p , 1 9 & ( R A s //a r @ o : t <e 1111.111.1 ,.'. 611; BS-;3 i #t e$ral /e/4ra#e 5r2te2$l@.a# i#te$ri#s ' e s /2 s 2 /e !.a';eri#sV ' ) $a5 F#.ti2# i .2##e7i #s% ; e /i ' e s r # 2 s 2 /e E 2 . a l . 2 # t a . t !Erite$ri#s% !i#te$ri#s% i#ter/e'iate Ei l a/e#ts 2005,RRE/AB,SITH ITB , 'nc t i o na l a nd no n, 'nc t i onal ad<esi)e ec<aniss 'sed b* anial cells in bindin0 to one anot<er and to t<e e8tracell'lar atri8. !he .unctional mechanisms are shown in epithelial cells, while the non.unctional mechanisms are shown in nonepithelial cells. A .unctional interaction is operationally defined as one that can e seen as a specialized region of contact y conventional andHor freeze&fracture electron microscopy. ,ote that the integrins and cadherins are involved in oth non.unctional and .unctional cell&cell +cadherins) and cell& matrix +integrins) contacts. !he cadherins generally mediate homophilic interactions, whereas the integrins mediate heterophilic interactions +see *igure 11&%D). )oth the cadherins and integrins act as transmemrane linkers and depend on extracellular divalent cations to function/ for this reason, most cell&cell and cell&matrix contacts are divalent&cationdependent. !he selectins and integrins can also act as heterophilic cell&cell adhesion molecules# the selectins ind to carohydrate, while the cell&inding integrins ind to memers of the immunogloulin superfamily. !he integrins and integral memrane proteoglycans that mediate non.unctional adhesion to the extracellular matrix are discussed later. E7tra.ellllar /atri7 9amm Proteoglycan Fibronectin P!%I))) tpilip i P0 elk. onoQ )'//#iggiii,isiononsinto*(omiriiii,Isl o tt ( 11 @ " rof)/'''0' 1 ' " ? 10'0 ''' <( ' 1. LL es ))) , )) 1 !lo li - 1 1 B3 ia It IC )))) 1$ (1))1)))))1+ ))+" <<< e#+ i<!t" ,k )) '16+1 =+ o i J 1 . 1 K 1 Figure A)F $n o!er!ie% of t*e macromolecular organization oldie e#tracellular matri#) .*e proteins and polysacc*arides s*o%n m t*is illustration %ill *e discussed in t*e follo%ing sections) .*e proteins depicted (ti*roneetin0 collagen0 and lamirin) contain binding sites t*e one anot*er0 as %ell as binding silo ft receptors (integrins) t*at are located at t*e cell surface) .*e pro teogl!cans are *uge protein-polysacc*aride completes t*at 3) copy muc* of t*e !olume of t*e e#tracellular space) " sat /atriks 'i lar sel @a#$ 4er4atasa# 'e#$a# /e/4ra# 5las/a- " /ateri 5e#$e/as @a#$ i#ert " E*M e$- Te#'2#, tla#$ l#ak, str2/a k2r#ea " 4er5era# 'ala/ /e#e#tka# 4e#tk 'a# aktiCitas sel- " /e/5erta;a#ka# k2#'isi sel @a#$ tela; ter'iEere#siasi 'a# /e/5erta;a#ka# ke/a/5a# sel #tk /e#$;asilka# 5r2'k#@a 2005,RRE/AB,SITH ITB !asal ebran "!M#$ 9aminin ntestin $ F-5:R ,,-,( =odel of t*e 4asal la/i#a- 3- D- Yr.;e#.2 a#' " * S.;itt#@, )LL0, FASO J. 4: )5((-)5L0) (P =:$da iat pit*elial s*eer 9:=3 Basal lamina Connecti!e ties >ie Connecti!e tisa#e Basal lem=a =uscle cell Plasm pit*elial .ell a membrane Basal laming 9el /idney glomarulue ndot*elial eel B9((( :R-3 $ 0IGURE 22-2) 6r$a#i:ati2# 2E t;e 4asal la/i#a i# 'iEEere#t tissues) la0 4i T;e basal laminae associated %it* endot*elial cells and muscle cells separate t*ese cells from t*e underlying or surrounding connecti!e tissueR (c) -n t*e +idney g9ernerulus0 bot* t*e endot*elium lining t*e capillanes and t*e epit*elium li#i#$ t;e urinary space form a basal lamina) T;s t*e fused basal lamina bet%een t*em is about t%ice as t*ic+ as t*at in ot*er tissues) Because bot* cell s*eets *a!e gaps in t*em0 t*is basal lamina is e#posed to bot* t*e blood and t;e ri#e ape#es and acts to filter capillary blood0 forming in t*e urinary space a filtrate t*at ultimately becomes %ine) $dapted from B $lberts at al)0 'JJ20 Molecular Biology of the Cell, 9' a', 5arland) p J(J' Me#$elili#$i sel 2t2t 'a# sel le/ak < 'i 4aBa; Far- e5itel, serta sel-sel e#'2teli/ " te/5at 5elekata# selA " s4strat #tk /i$rasi sel " /e/4atasi Fari#$a# 'ala/ sat 2r$a#, " se4a$ai sat 4arier /akr2/2lekl < #tk i#Casi sel ke sat Fari#$a# 2005,RRE/AB,SITH ITB