Ac#n%Binding%Proteins%&%Microtubule%Associated%Proteins%%%%Last%Class:%%Microtubule%dynamics!For!high-quality!reviews!on!the!ac5n!and!microtubule!cytoskeletons,!see!YouTube!lectures!from:!UC!Berkeley!(ac5n)!Tim!Mitchison!(microtubules)!Tony!Hyman!(microtubules)!!In!general,!the!lectures!on!the!iBiology!channel!(iBioSeminars)!are!excellent.!Reminder:%The%study%of%ac#n%and%microtubules%has%been%aided%by%using%drugs%that%affect%polymer iz a# on%GFP-tubulin!RFP-ac5n!Which%drug%was%used%to%treat%this%cell%?%hMp://www.youtube.com/watch?v=aABEbn2t0Y4!Today:%How%are%ac#n%filaments%and%microtubules%organized%by%their%binding%partners%?!I!Know!You!Can’t!Read!This!!Ac#n%binding%proteins%(ABPs)%control%the%assembly,%disassembly,%organiza# on,%and%movement%of%ac# n%fi lam ents%(binds!monomers)! (binds!monomers)!(binds!monomers!&!filaments)!(binds!monomers!&!filaments)!Formins%Arp2/3%complex%Thymosin%β4%Profilin%Ac#n%binding%proteins%(ABPs)%control%the%assembly,%disassembly,%organiza# on,%and%movement%of%ac# n%fi lam ents%Cofilin%Gelsolin%CapZ%Tropomyosin%Fimbrin%α-ac#nin%Filamin% Spectrin%ERM%proteins%%Control%of%polymeriza#on%and%depolymeriza#on:%monomer!sequestering!proteins!nuclea5ng!factors!capping!proteins!stabilizing!proteins!depolymerizing!proteins!severing!proteins!!Organiza#on%of%filaments:%%network!forming!crosslinking!proteins!bundle!forming!crosslinking!proteins!membrane!linker!proteins!!Movement%of%filaments:%motor!proteins!Ac#n%binding%proteins%perform%a% v ariety%of%func# ons%Capping%proteins%stabilize!filaments!by!binding!to!their!ends.!Filaments!are!stabilized!because!!the!capping!proteins!prevent!addi5on!or!loss!of!subunits!from!the!filament!ends.!!Examples!include!CapZ,!which!caps!the!(+)!end!of!filaments,!and!tropomodulin,!which!caps!!the!–!ends!of!ac5n!filaments.!!(Can!you!think!of!another!group!of!proteins!that!caps!the!!(–)!ends!of!filaments?)!!Stabilizing%proteins%bind!along!the!length!of!filaments.!Tropomyosin!is!a!long!snake-like!!molecule!that!binds!several!subunits!along!the!filament!and!stabilizes!the!polymerized!!state.!!Severing/Depolymerizing%proteins%disassemble!ac5n!filaments!and!higher!order!structures.!!The!assembly!of!ac5n!filaments!in!the!cell!must!be!balanced!by!filament!disassembly,!!which!maintains!the!monomer!pool!and!thus!replenishes!the!substrates!for!!polymeriza5on.!A!protein!called!cofilin!enhances!the!rate!of!ac5n!depolymeriza5on!by!!severing!ac5n!filaments!and!crea5ng!more!(–)!ends.!A!protein!called!gelsolin!also!severs!ac5n!!filaments!and!breaks!them!into!short!fragments.!A_er!severing,!gelsolin!remains!bound!!to!the!+!end!of!the!filament.!The!severing!ac5vity!of!gelsolin!is!ac5vated!by!increases!in!!the!intracellular!concentra5on!of!Ca+2.!Ac#n%binding%proteins%cap,%stabilize,%sever,%and%depolymer iz e %filam e nts%D.Drubin!ABPs%control%the%assembly,%disassembly,%and%%organiza#on%of% ac #n%filaments%?%Ac#n%binding%proteins%organize%ac#n%filaments%into%bundles%and%networks%and%link%ac#n%filaments%to%membranes%Cross-linking%proteins%typically!have!two!ac5n-binding!domains!separated!by!spacer!domains!of!different!lengths!to!produce!assemblies!with!different!architectures.!!!Cross-linking!proteins!with!longer,!more!flexible!spacers!usually!func5on!to!arrange!filaments!into!gel-like!networks.!These!include!filamin!and!spectrin.!Some!ac5n-binding!proteins!have!mul5ple!func5ons.!For!example,!the!Arp2/3!complex!can!nucleate!and!cross-link!ac5n!filaments.!!Cross-linking!proteins!with!shorter,!more!rigid!spacers!tend!to!bundle!filaments!into!aligned!arrays.!Bundling!proteins!with!very!short!spacers!(fimbrin,!villin,!and!fascin)!o_en!lead!to!5ght,!parallel!arrays.!α-ac5nin,!with!its!somewhat!longer!spacer,!can!crosslink!filaments!into!the!looser,!parallel!and!an5-parallel!arrays!involved!with!contrac5on.!!Membrane-ac#n%linker%proteins%aMach!the!ac5n!cytoskeleton!to!the!plasma!membrane.!The!simplest!connec5ons!entail!indirect!interac5ons!between!integral!membrane!proteins!and!ac5n!filaments.!These!interac5ons!are!o_en!mediated!by!peripheral!membrane!proteins!such!as!the!ERM!proteins!(e.g.,!ezrin),!which!act!as!a!linker!between!F-ac5n!and!the!integral!membrane!proteins.!Spectrin!also!connects!ac5n!to!membrane!proteins.!Dystrophin!links!cor5cal!ac5n!to!muscle!cell!membranes!via!the!Dystroglycan!complex.!!ABPs%organize%ac#n%filaments%ABPs%link%ac#n%filaments%to%membranes%Many!ac5n!structures!are!found!at!the!cell!periphery!in!the!ac5n-rich!layer!just!beneath!the!plasma!membrane!called!the!cell%cortex.!This!layer!gives!an!animal!cell!mechanical!strength!and!enables!it!to!form!surface!structures!and!perform!surface!movements!(phagocytosis,!cytokinesis,!and!locomo5on).!The!spectrin-based!membrane!skeleton!lies!immediately!adjacent!to!the!plasma!membrane.!Ezrin!links!bundled!ac5n!to!the!membrane!in!microvilli.!Fimbrin,%Villin%ABPs%and%disease%Muta5ons!in!the!genes!encoding!proteins!of!the!red!blood!cell!membrane!skeleton!(spectrin,!ankyrin,!band4.1)!can!result!in!cells!that!rupture!easily,!giving!rise!to!diseases!known!as!hereditary!spherocy5c!anemias.!Muscular!dystrophies!are!gene5c!diseases!o_en!characterized!by!the!progressive!weakening!of!skeletal!muscle.!!Duchenne!muscular!dystrophy!(DMD)!affects!the!protein!dystrophin.!!Without!func5onal!dystrophin,!the!plasma!membrane!of!muscle!cells!weakens!and!eventually!ruptures.!Microtubule%associated%proteins%(MAPs)%control%the%assembly,%disassembly,%organiz a# on,%and%movement%of%mic r otubule s%γ-TURC%Stathmin%+TIPS%Microtubule%associated%proteins%(MAPs)%control%the%assembly,%disassembly,%organiz a# on,%and%movement%of%mic r otubule s%Kinesin-13%Katanin%MAPs%XMAP215%Tau%MAP-2%Plec#n%Microtubule%associated%proteins%perform%a% v ariety%of%func#
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