Study guide, Chapter 20 pt 1-3 PDF

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GCD$3033$$$ $$ Cell$Biology$Study$Guide$ ECB$Chapter$20$‐$Cellular$Communities$

Spring$2012$$

$ Tuesday$pp$689$–$707:$Tissues$ Thursday$pp$707$–$717:$Stem$cells$ Tuesday$pp$717$–$729:$Cancer$ $ Cells$of$multicellular$organisms$such$as$ourselves$are$organized$into$tissues,$which$can$be$ defined$as$collections$of$cells$and$their$surrounding$extracellular$matrix$that$function$as$an$ organized$group$to$perform$a$specific$function.$In$animals,$the$four$major$tissue$types$are$ epithelial,$muscular,$nervous,$and$connective$tissue.$This$chapter$emphasizes$epithelial$and$ connective$tissue$to$describe$1)$how$cells$are$organized$into$tissues;$2)$the$components$and$ functions$of$extracellular$matrix;$3)$the$renewal$of$tissues$by$stem$cells;$4)$how$cells$can$ escape$from$the$controlled$organization$of$tissues$to$give$rise$to$cancers.$ $

Connective$Tissue$ Connective$tissue$is$the$largest$and$most$diverse$tissue$type.$Bone,$cartilage,$fat,$blood$and$ the$dermal$layer$of$skin$are$examples$of$specialized$types$of$connective$tissue.$In$addition,$ our$internal$organs$and$structures$like$blood$vessels$and$nerves$are$surrounded$by$a$fine$ layer$of$connective$tissue,$which$provides$support$and$protection$to$these$structures.$This$ supporting$role$is$a$general$feature$of$connective$tissue.$Although$all$tissues$are$composed$ of$both$cells$and$ECM,$in$connective$tissues$the$ECM$plays$an$especially$prominent$role$and$ is$responsible$for$many$of$the$properties$of$these$tissues.$$ $ Extracellular$matrix$(ECM)$consists$of$fibers$embedded$a$gel‐like$material$called$ground$ substance.$Think$of$rebar$embedded$in$cement,$only$more$flexible.$The$fibers$provide$tensile$ strength$(resistance$to$stretching)$and$some$degree$of$flexibility,$and$the$ground$substance$ provides$resistance$to$compressive$forces.$ $

ECM$fibers$ The$major$fiber$of$the$ECM$is$collagen.$About$25%$of$all$animal$protein$is$collagen,$making$it$ the$most$abundant$protein$of$our$body.$Most$of$this$is$type$I$collagen,$which$assembles$into$ long,$strong,$stiff$extracellular$fibers.$These$fibers$have$an$interesting$structure$and$ formation.$Individual$collagen$polypeptides,$known$as$alpha$chains,$assemble$into$a$triple‐ helical$procollagen$molecule$inside$the$cell$during$its$passage$through$the$secretory$ pathway.$These$triple$helices$contain$pro‐peptides$at$their$ends,$which$prevent$further$ assembly$inside$the$cell.$Once$secreted$into$the$extracellular$space,$the$pro‐peptides$are$ cleaved$and$many$thousands$of$collagen$molecules$assemble$in$a$highly$ordered$manner$ into$~100$nm$collagen$fibrils.$These$fibrils$in$turn$become$organized$into$bundles$of$fibers$ that$ultimately$can$be$much$larger$than$the$cell$that$produced$them$(see$Figure$20‐9).$The$ strength$of$the$fibers$is$increased$through$crosslinks$between$the$individual$collagen$

molecules.$Many$genetic$disorders$are$caused$by$mutations$in$genes$that$code$for$collagen$ or$the$proteins$that$contribute$to$its$synthesis$and$assembly.$$ $ In$addition$to$Type$I$collagen,$there$are$about$30$other$recognized$types$of$collagen,$each$ with$a$specialized$structure$and$function.$For$example,$Type$IV$collagen$assembles$into$a$2‐ dimensional$meshwork$found$in$the$basal$lamina$that$supports$epithelial$cells.$Another$ specialized$type$of$collagen$is$found$in$cartilage.$ $ Elastic$fibers$are$the$second$major$type$of$fiber$found$in$the$ECM.$These$fibers$are$made$of$ a$highly$coiled$protein$called$elastin,$which$has$special$properties$that$allow$it$to$stretch$and$ contract.$These$fibers$are$highly$abundant$in$blood$vessels,$which$must$expand$or$contract$ to$control$blood$pressure.$They$are$also$required$for$the$ability$of$skin$to$properly$stretch.$$ $ Most$cells$are$capable$of$synthesizing$a$small$amount$of$collagen$and$other$ECM$fibers.$ However,$a$type$of$connective$tissue$cell$called$the$fibroblast$is$specialized$for$this$purpose.$ These$cells$are$capable$of$migrating$through$connective$tissue$spaces$and$can$synthesize$ many$components$of$the$ECM.$Fibroblast$migration$plays$an$important$role$during$wound$ healing,$when$synthesis$of$new$ECM$is$required$to$repair$damaged$tissue.$Fibroblasts$also$ control$the$arrangement$of$the$fibers$they$synthesize,$for$example$organizing$type$I$ collagen$into$plywood‐like$sheets$in$bone$and$dermis,$or$into$long$parallel$strands$in$the$case$ of$tendons$(see$Figures$20‐12,13;$Movie$20.1).$$ $ Cells$attach$to$components$of$the$ECM$using$two$types$of$molecules.$A$large$family$of$ membrane‐spanning$receptor$proteins$called$integrins$are$capable$of$binding$to$both$ intracellular$components$of$the$actin$cytoskeleton$and$to$extracellular$components$of$the$ ECM.$Many$integrins$interact$with$an$ECM$protein$called$fibronectin.$Fibronectin$has$the$ ability$to$bind$many$different$ECM$components$through$multiple$independent$domains,$so$it$ acts$as$a$sort$of$glue,$linking$integrins$to$collagen$fibers,$and$binding$collagen$fibers$to$each$ another$and$to$other$ECM$molecules.$ $ In$addition$to$serving$a$structural$role,$integrins$also$act$as$signaling$molecules.$When$ integrins$bind$an$ECM$substrate,$they$can$activate$signaling$cascades$inside$the$cell;$ integrin/ECM$interactions$can$also$cause$the$integrin$molecule$to$bind$more$actively$to$the$ cytoskeleton.$Conversely,$the$binding$of$integrins$to$fibronectin$and$other$extracellular$ molecules$can$be$stimulated$by$attachment$of$integrins$to$the$actin$cytoskeleton$as$well$as$ from$other$signals$from$inside$the$cell$(see$Figure$20‐15).$ $

Ground$substance$ The$extracellular$space$of$connective$tissue$that$is$not$occupied$by$fibers$is$referred$to$as$ ground$substance.$Some$connective$tissues$(dermis,$tendons)$are$so$packed$with$fibers$that$ there$is$very$little$ground$substance.$In$other$cases,$such$as$the$jelly‐like$interior$of$the$eye,$ the$ground$substance$makes$up$the$majority$of$the$tissue.$Ground$substance$is$mostly$ water,$and$contains$a$number$of$highly$glycosylated$proteins$called$proteoglycans$that$give$ it$a$gel‐like$property$and$help$it$to$resist$compression.$These$molecules$consist$of$a$core$

protein$linked$to$multiple$polysaccharide$molecules$called$glycosaminoglycans$(GAGs).$ GAGs$are$long$chains$consisting$of$hundreds$of$repeating$disaccharide$units,$many$of$which$ contain$negative$charged$carboxyl$or$sulfate$groups.$These$multiple$negative$charges$are$ key$to$the$gel‐like$properties$of$proteoglycans:$they$attract$cations$that$draw$in$water$ through$osmotic$forces,$creating$the$swelling$pressure$that$resists$compression.$The$ negative$charges$also$cause$the$GAG$molecules$to$remain$unfolded,$taking$up$more$space:$ proteoglycans$can$form$aggregates$that$approach$the$size$of$individual$cells$(see$Figure$20‐ 17).$GAGs$also$regulate$the$movement$of$other$molecules$through$the$extracellular$matrix,$ acting$as$a$physical$filter$in$some$cases$and$affecting$the$diffusion$of$growth$factors$and$ other$molecules.$$ $ Several$enzymes$are$capable$of$digesting$the$proteoglycans$and$collagen$fibers$of$the$ECM,$ and$migrating$cells$exploit$these$enzymes$to$help$them$move$through$connective$tissue$ spaces.$Although$this$can$be$beneficial$in$some$cases,$the$movement$of$both$metastasizing$ tumor$cells$and$invading$microorganisms$is$assisted$by$degradation$of$ECM$components.$$ $

Connective$tissue$cells$ Cells$of$the$connective$tissue$also$help$to$support$other$tissues.$Fibroblasts$synthesize$most$ ECM$components$of$connective$tissues.$$These$are$highly$motile$cells$capable$of$migrating$ to$sites$of$injury.$$Fat$cells$(adipocytes)$store$energy$in$the$form$of$triglyceride$droplets.$ They$also$serve$a$cushioning$role$for$internal$organs,$and,$in$the$case$of$brown$fat,$can$ generate$heat.$A$variety$of$cells$of$the$immune$system$migrate$through$connective$tissue$ spaces,$helping$to$rid$the$body$of$debris$and$foreign$substances.$These$include$ macrophages,$plasma$$cells$and$mast$cells.$$$ $

Epithelial$tissue$ All$of$the$internal$and$external$surfaces$of$our$body$are$covered$by$an$epithelial$lining.$ Epithelial$cells$also$form$the$functional$parts$of$secretory$organs$such$as$the$pancreas,$ salivary$and$sweat$glands,$and$are$specialized$for$absorption$in$the$gut$and$for$gas$diffusion$ in$the$lung.$The$shape$and$organization$of$epithelial$cells$varies$widely,$from$single$to$ multiple$layers,$and$from$tall$(columnar)$to$squat$and$flattened$(squamous).$Two$properties$ of$epithelia$make$them$especially$suited$to$their$functions:$a$distinct$apical‐basal$polarity,$ and$the$presence$of$specialized$intercellular$junctions.$$ $ Differences$between$the$apical$and$basal$surfaces$of$epithelial$cells$are$critical$to$their$ functions.$Unlike$connective$tissue,$epithelia$have$no$blood$supply,$and$must$receive$ nutrients$by$diffusion$from$underlying$connective$tissue.$This$occurs$through$their$basal$ surface,$which$attaches$to$connective$tissue$through$the$a$thin$sheet$of$connective$tissue$ called$the$basal$lamina.$This$connection$involves$interactions$between$integrins$of$the$basal$ cell$membrane$of$the$epithelial$cell$and$a$fibronectin‐like$protein$called$laminin$within$the$ basal$lamina.$The$basal$lamina$contributes$to$the$epithelial$barrier$to$microorganisms$but$ allows$diffusion$of$essential$gases$and$nutrients.$The$apical$surface$of$epithelial$cells$can$be$ specialized$for$secretion,$absorption,$or$other$functions,$and$the$secretory$and$endocytic$

systems$can$be$organized$to$direct$vesicle$movement$in$one$direction$or$the$other.$The$ absorptive,$secretion$or$ion$conductance$capacity$of$some$cells$can$be$supported$by$a$ dramatic$increase$in$area$of$these$surfaces,$through$the$presence$of$basal$infoldings$or$ apical$microvilli.$$ $ Five$major$types$of$cell‐cell$junctions$commonly$found$in$epithelia$are$shown$in$Figure$20‐22.$$ Each$of$these$junctions$has$a$specific$function,$is$comprised$of$unique$sets$of$proteins,$and$ interacts$with$a$defined$set$of$cytoskeletal$proteins.$ $ Name$ Function$ Components$ Cytoskeletal$links$ Tight$junction$ Continuous$barrier$to$ Claudins$and$ ‐$ diffusion$between$cells$ occludins$ near$apical$surface;$ separates$apical$and$ basal$membrane$ domains$ Adherens$ Continuous$mechanical$ Cadherin$ Actin$filaments$via$ junction$ attachment$between$ family$ linker$proteins$ cells$near$apical$surface$ proteins$$ Desmosome$ Mechanical$attachment$ Cadherin$ Intermediate$ between$cells$like$a$ family$ filaments$(keratins)$ “spot‐weld”$ proteins$$ via$linker$proteins$ Gap$junction$ Forms$aqueous$ Connexins$$ ‐$ channel$allowing$ selective$passage$of$ molecules$between$ cells$(...