Term
| Functions of the Cytoskeleton |
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Definition
Support of the cell - Intermediate filaments
Support of the membrane - Actin filaments
Targeted Delivery - Microtubules |
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Term
| Monomers (G-Actin)- 'G' refers to 'globular' |
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Definition
Molecular weight ~ 43 kDa (4-5 nm in diameter)
Binds ATP or ADP
Innate ATPase activity |
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Term
| Polymers (F-Actin) - 'F' refers to 'filamentous' |
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Definition
Diameter 7-9 nm
Two helical strands (periodicity of one strand ~ 72 nm)
Innate ATPase activity (enhanced within filaments)
Polarized filaments (due to ATP hydrolysis) |
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Term
| Steady state of F-Actin (Critical Concentration) |
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Definition
| rate of monomers coming on is equal to the rate of monomers coming off |
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Term
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Definition
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Term
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Definition
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Term
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Definition
| added to positve side, falls of negative side. |
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Term
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Definition
| Filament Depolymerization - barbed-end blocking (caps barbed positive end of filament) |
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Term
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Definition
| Filament Depolymerization - monomer binding |
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Term
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Definition
| Filament Stabilization - lateral binding - fluorescence-tagged, used for observation |
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Term
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Definition
| Filament Stabilization - lateral binding (cell permanent) |
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Term
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Definition
Biochemical method for measuring Actin polymerization
- formation of filamentous actin increases viscosity |
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Term
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Definition
Biochemical method for measuring Actin polymerization
- F-Actin pellets at 100,000 xg for 30 minutes |
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Term
| Fluorescence Video Microscopy |
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Definition
Biochemical method for measuring Actin polymerization
- optical measurements of filament growth |
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Term
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Definition
Biochemical method for measuring Actin polymerization
- Actin-pyrene fluroescence intensity (intensity is increased in filamentous actin - 20 fold increase) |
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Term
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Definition
Nucleation of Actin Filament
- forms orthogonal/branched arrays of Actin filaments
- set of seven proteins
- mimics an "actin nucleus" |
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Term
| Formin Family of Nucleating Proteins |
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Definition
Nucleation of Actin Filament
- forms bundles of parallel Actin filaments |
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Term
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Definition
Nucleation of Actin Filaments
- binds, orients, and stabilizes Actin nuclei |
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Term
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Definition
| Dimer of Formin - de novo nucleation and processive monomer addition |
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Term
| Arp: actin-related protein |
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Definition
- high degree of homology with actin
- form identical folds as found in actin |
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Term
| Properties of Arp2/3 complex |
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Definition
1. Lateral F-Actin binding
2. de novo Actin nucleation
3. Pointed-end Actin binding |
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Term
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Definition
activates Arp2/3 complex
- activated by cdc42 (small GTPase protein) and PIP2 |
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Term
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Definition
Small Actin Binding Protein
- enhances barbed-end addition
- 12-15 kDa
- localized at membranes
- Binds to PIP2
- regulated by phosphorylation
- blocks pointed end addition
- promotes barbed end addition
- accelerates ADP-ATP exchange
- lowers Km at the barbed end |
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Term
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Definition
Small Actin Binding Protein
- buffers available monomers
- ~ 5 kDa
- very abundant protein (up to 0.5 mM in some cell types
- enriched at cell periphery
- inhibits monomer addition
- inhibits nucleotide exchange
- inhibits nucleotids hydrolysis
- G-Actin buffer (regulated by mass action) |
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Term
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Definition
Small Actin Binding Protein
- pointed-end severing
- 15-22 kDa
- Activates monomer binding, pointed end capping, filament binding (ADP-actin >> ATP-Actin), filament severing (twisting)
- net effect: - end depolymerization
- inhibited by: acidic/neutral pH, phosphorylation (ser-3), PIP2-(4,5), tropomyosin |
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Term
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Definition
Actin Capping Protein
- barbed end capping (+ end)
- moderates direction polymerization |
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Term
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Definition
Actin Capping Protein
- pointed end capping (- end)
- caps and protects |
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Term
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Definition
Lateral Actin Binding Protein
- stiffens filaments
- stabilizes tropomodulin-actin
- impedes cofilin binding
- covers ~ 6 actin monomers
- enhances myosin II binding
- sterically hinders numerous lateral actin interactions |
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Term
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Definition
Actin Bundling Proteins
- two actin binding domains
- "dense" filament bundling (~12 nm) |
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Term
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Definition
Actin Bundling Protein
- single actin binding domains
- antiparallel coiled coil tail domain interactions
- "loose" filament bundling (~35-60 nm; stress fibers) |
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Term
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Definition
| occurs with disruption of the membrane-cytoskelton linkage |
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Term
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Definition
| Binds Na+ channels to spectrin (fodrin) which is bound to F-Actin |
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Term
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Definition
- tetramer from head-to-head heterodimers
- tetramer extends 200 nm
- chain formed of 106 aa repeats
- multiple membrane protein interactions
- actin association via protein 4.1 at tail |
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Term
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Definition
- Actin binding (CH) domain
- six Ig-like repeat domains
- self-association via 6th repeat
- multiple membrane protein interactions
- crosslinks orthogonal actin arrays
- concurrently binds F-Actin and various integral membrane proteins |
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Term
| Filamin mutant melanocyte |
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Definition
Filamin (ABP-280) deficient cells
- continuous blebbing
- diminished locomotion
- viable |
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Term
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Definition
| Constituitive membrane Blebbing |
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Term
| Duchenne Muscular Dystrophy |
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Definition
mutation in the dystrophin gene
- x-linked recessive mutations
- 1 in 3,500 males
- 100s of distinct mutations identified
- most result in loss of protein
- progressive muscle weakness and atrophy
- sarcolemmal membrane and fiber damage
- ~12 y.o = wheelchair bound
- ~18 y.o = death by pulmonary failure
- subset have cardiomyopathy |
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Term
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Definition
- Gene: 2.6 x 10^6 base pairs (largest in human genome)
- 427 kDa protein
- expressed in skeletal and cardiac muscle
- some expression in neurons
- binds F-Actin
- binds B-dystroglycan |
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Term
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Definition
- provides a mechanical link between the actin
- provides a structural support against the mechanical stress from repeated contraction and relaxation |
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