cytoskeleton - tulane universitywiser/mcbp607/skeleton1.pdf · three major filamentous systems of...
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Cytoskeleton
Mark Wiser
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Mitochondria
PlasmaMembrane
NucleusLysosome
ER
Golgi
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Three Major Filamentous Systems of the Cytoskeleton
IF proteinsrope-like fibers (~10 nm)
intermediate filaments
tubulin + associated proteins
tubular structures (25 nm) microtubules
actin + associated proteins
thin filaments (6-7 nm) microfilaments
Protein Composition
Description (diameter)
CytoskeletalElement
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Actin and Microfilaments• highly conserved globular protein (G-actin)• polymerizes into thin filaments (F-actin)
• exhibits polarity (+ and – ends)• (barbed and pointed ends)
• filaments stabilized by other proteins
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Actin Polymerization• requires nucleation (activation)• elongation primarily at “+” end (= barbed end)• ATP/ADP
• G-actin has bound ATP• ADP-actin more likely to dissociate
• actin-binding proteins• monomer sequestration (eg., profilin)• capping proteins (eg., gelsolin)
• cellular regulation• rho family (ras-like G-proteins)• trimeric G-protiens
• drugs• cytochalasins (prevent assembly)• phalloidin (prevent disassembly)
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Examples of Actin-Binding Proteins
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Membrane Interactions
• submembrane cytoskeleton (eg., RBC)• focal adhesions (ECM interactions)• adherens junctions (cell-cell interactions)
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Focal Adhesions
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Myosin and Force Generation
• large family of proteins (16)• actin-activated ATPase• converts chemical energy
into mechanical energy
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Ameboid Movement
• reorganization of cytoskeleton in pseudopodia
• force for protrusion?• force for traction?
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MicrotubulesMajor Roles:1. Mechanical/Cell Shape2. Mitotic Spindle3. Cilia/Flagella
Tubulin:• highly conserved• heterodimer (α, β)• in vivo assembly
from MTOC
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Microtubule Organizing Centers• centrioles
• aka basal bodies of flagella• barrel-shaped (triplets of µT)
• centrosomes• amorphous matrix (± centrioles)• organizes cytoplasmic µT array• forms spindle during cell division
• spindle pole bodies• located on nuclear membrane• forms mitotic spindle in many
lower eukaryotes
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microtubules + microribbons
lateral crest containing actin and myosin
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Flagellar Movement
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Motor ProteinsµF associated
• myosin
µΤ associated
• dynein– cilia/flagella– cytoplasmic
• kinesin
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Kinesins• large superfamily of proteins
– defined by 'motor' domain• tail regions highly divergent (function)• chemomechanical cycle
– similarities to myosin– two motors needed
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Kinesins and Mitosis• reorganization of µT during mitosis
– disassembly of cytoplasmic µT– assembly of spindle apparatus
• duplication of centrosome to form spindle apparatus
• at least 4 kinesins implicated– separation of poles– migration of chromosomes
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possible kinesin roles:• stabilize metaphase plane• sliding µT to drive poles apart• pull asters toward membrane• kinetochore: chromosome
movement
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Intermediate Filaments• rope-like fibers extending
from nucleus periphery• extremely stable
– resistant to detergent extraction
• only in metazoa• subunits are part of large
multigene family– related to nuclear lamins– tissue specific expression
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Intermediate Filament Proteins
60-70nuclear laminalamins (A, B, C)V57-150neuronsneurofilamentIV
51glial cellsGFAP52muscledesmin53mesenchymalvimentinIII
50-70epithelialbasic-neutral keratins
II40-60epithelial acidic keratinsI
Size (kDa)Cell TypeExamplesType
heptad repeatshead tail
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IF Proposed Structure
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IF Function• mechanical support
• abundant in cells and structures under mechanical stress (eg, epithelia, hair, nails, muscle, etc)
• genetic defects linked to keratin: epidemolysis Bullosa simplex, epidermolytic hyperkeratosis
• links to membranes and other cytoskeletal elements
• specialized function in differentiated cells• tissue specific expression• markers for tumor diagnosis