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42 Cards in this Set

  • Front
  • Back

Skeletal muscle

- Multinucleated


- Formed by fusion of myoblasts (muscle cell precursors)


- Myofibril consists of contractile units (sarcomeres)



Cytoskeleton

Three dimensional filamentous protein network that gives cells shape and organize cell parts



Three major types of cytoskeleton protein filaments

1) Actin filaments


2) Microtubules


3) Intermediate Filaments

Actin Filaments

*Protein filament that form cytoskeleton


- Two stranded helical polymers of actin


- Diameter: 5-9nm


- Function: cell shape, cellular extensions, contractile ring, muscle contract

Microtubules

*Protein filament that form cytoskeleton


- Hollow cylinders made of tubulin


- Diameter: 25nm


- Function: Mitotic spindles, positioning of organelles

Intermediate filaments

*Protein filament that form cytoskeleton


- Rope-like fibers made of intermediate filament proteins


- Diameter: 10nm


- Function: giving cells mechanical strength (nuclear lamina)

Actin

*Globular ATP binding protein that can exist as...


1) G-Actin


2) F-Actin


- Polarity can be visualized using fragment of myosin to label actin filaments


- In living cell, filaments are further cross linked and bundled to form large scale actin structures

G-Actin

*Globular actin (monomer)


- Assembles in head-to-tail manner producing filaments with a distinct polarity


- Consists of two protofilaments that twist around each other

3 stages of actin filament dynamics

1) Lag phase (formation of initial aggregation; nucleation-- rate limiting step; seed)


2) Elongation (growth; proceeds quickly once seed is present)


3) Steady state (no net growth --CC)

Critical concentration (CC)

- Concentration of free subunit G-actin at steady state (no net growth/disassembly)

"Treadmilling"

Net flux of subunit through polymer in actin filament

ATP bound form (T-form)

Most free actin subunits are in this form


- Favors assembly


- Tip of polymer remains in this form

ADP bound form (D-form)

ATP is hydrolyzed to this form after its assembly into a filament due to its reduced binding affinity for its neighbors


- Favors disassembly

Actin related proteins (ARPs)

- Structurally similar to actin



Arp2/3 complex

- Protein complex that promotes nucleation of actin filaments


- Promotes branching of actin filaments


- Binds to side of filaments (often seen at leading edge of migrating cells)

Actin binding proteins

*Regulate actin dynamics


1) actin related proteins (ARPs)


2) formins


3) G-actin binding proteins


4) Capping proteins

Formins

*Actin binding protein; regulates actin dynamics


- binds to (+) end


- dimeric protein


- nucleate formation of new actin filament by capturing two actin monomers


- Remain associated with growing (+) end as it elongates but allows binding of new subunits

G-actin binding proteins

*Actin binding protein; regulates actin dynamics


- Proteins that bind free subunits affect filament assembly


- Bonded with thymosin- blocks assembly


- bonded with profolin- promotes assembly

Thymosin

Binds to G-actin to block assembly


- No binding to ends of actin filaments


- No ATP-->ADP exchange

Profolin

Binds to G-actin and promotes assembly

Capping proteins

*Actin binding protein; regulates actin dynamics


- Proteins that bind to filament ends can affect filament dynamics


- Binds with CapZ at (+) ends; prevents assembly and disassembly to stabilize actin filament


- Binds at (-) ends with ARP or tropomodulin in muscle cells

Stress fiber

Actin cells organized into contractile bundles


- a-actinin


- loose packing of actin filament

Filopodium

Actin cells organized into tight bundles


- fimbrin


- close packing of actin filament

Cell cortex

Actin cells organized into gel network


- filamin


- Clamping together two actin filaments, formation of viscous gel or web

Myosin motors

*Actin based motors that move toward (+) end of actin filaments


- Contain head, neck, tail

Head

*Myosin general feature


- Binds actin and possesses ATPase activity

Neck

*Myosin general feature


- Binds light chains and is important for conformational changes

Tail

*Myosin general feature


- Binds to cargo that determine the function of each myosin motor

Myosin II

Muscle contraction, cell shape, and motility

Myosin based motility

- Unidirectional (-) --> (+)


- use ATP


- myosin conformational change coupled with changes in binding affinity to actin

Mechanism of myosin based motility

1) Myosin head ATTACHED to rigar stone


2) ATP binding causes myosin to RELEASE actin filament


3) Hydrolysis of ATP COCKS head and results in weak binding of actin molecules


4) Weak binding cause release of PO4- tight binding/"power stroke" (FORCE GENERATING)


5) Release of ADP returns myosin to rigar state (ATTACHED)

Sarcomere

Basic unit of muscle organization

Muscle contraction depends on...

ATP-driven sliding of actin filament against myosin II filaments

Actin

Thin actin filament

Myosin II

Think filament

a-actinin

bundles actin filaments in Z-discs

CapZ

Caps actin filaments at (+) end

Tropomodulin

Caps actin filaments at (-) end

Titin

elastic protein holds myosin II in place

Nebulin

Dictates the length of actin filaments (molecular ruler)

Motor neuron signal

Induces muscle contraction


- Triggers sudden rise in cytosolic concentration of Ca2+

Troponin

Binds Ca2+ and pulls tropomyosin out of its normal position