Download Lecture 17 Outline Cell Motility: Encompasses both changes in cell

Lecture 17 Outline
Cell Motility: Encompasses both changes in cell location and more limited movement of
parts of the cell. Requires interactions of cytoskeleton with motor proteins, utilizes ATP
Motor Proteins: Bind and hydrolyze ATP- Results in Conformational Change within the
Motor Protein. Unidirectional movement involves coupling of mechanical events with
chemical events. Bind Polarized Filaments Function by: 1. Movement along Tracks ( i.e.
Movement of Mitochondria) 2. Cause Filaments to Slide against One Another (i.e.
Muscle Contraction) Different Motor Proteins Differ in: The Type of Filament They
Associate (Actin or Microtubule) The Direction of Movement (Plus End or Minus End
Directed), The “Cargo” they carry
Microtubule Based Movement
Motors: Kinesin ( Plus end directed) and Dynein (Minus end directed motors)
Kinesin- plus End Directed Away from Centrosome. Two Globular heads- bind /
hydrolyze ATP and bind MT. Middle Flexible domain, mediates dimerization, Tail for
binding cargo- Specific. Highly processive. Roles in Axonal transport, cell polarization,
Arrangement of ER.
Dynein- Processive -Fastest Motor Protein, Large Motor Protein. Similar Two globular
heads bind ATP and MT. Role in Motion of Cilia and Flagella, Localize Golgi.
Mechanism of Dynein walking along MT.1) Leading Head Attaches to a beta Tubulin
(No ATP). Now Leading Head Binds ATP Trailing Head Propelled Forward Past
Leading Head. ADP Release From New Leading Head and Hydrolysis of ATP by New
Lagging Head. Cycle Can Begin Again- has Moved One Step.
Roles of Kinesin and Dynein: Cell Polarization is a Reflection of the Polarized
System of Microtubules in the Cell Interior. Movement along MT tracks takes different
cargos- vesicles for release from axon. Requires processive Kinesin .
Microtubule Motor Proteins Help Arrange Membrane Enclosed Organelles in
Eukaryotes- Inhibition of MT polymerization- ER ends up by centrosome and Golgi falls
apart. Association of motor proteins with proteins on outside of vesicle membrane allows
for interactions. Cilia and Flagella-unique 9+2 arrangement of MT. MTOC is basal body
at base of cilia or flagella. Undulating movement of flagella and rowing oar like
movement of cilia different but mechanism same. Key is axonemal dynein that can bind
MT at head and tail. Cross bridges between the neighboring tubule pairs ( via Nexin
protein) allows movement of ciliary dyneins to not cause sliding of one filament over
other, instead, bending of cilia or flagella.
Microfilament based Movement
Motors: Myosins Superfamily of myosin proteins- globular head binds ATP and actin.
Myosin II (conventional myosin) involved in contraction of skeletal muscle. Myosin I –
single head- nonprocessive – movement of cargo, or associate with cortical actin to
influence cell shape. Myosin II – important in muscle contraction, forms bipolar myosine
filament- as many as 300 myosin heads per filament. Shortening of Sarcomere ( Z-Disc
to Z-Disc) Upon Contraction, Length of Filaments Remains Unchanged, Thin (Actin)
Filaments And Thick ( Myosin) Filaments Slide Across One Another, Bipolar Myosin
Filament Walks to the Plus End of Actin Filament (Z-Disc) Structural Components of
Sarcomere Titin, Nebulin alpha- actinin, CapZ, Tropomodulin. Regulatory Components
Tropomyosin, Troponin, Ca2+. Actin Filament Stability Requires: CAP Z- Cap Plus End
of Actin Filament, Tropomodulin- Cap Minus Ends of Actin Filament. Nebulin- stabilize
actin filament- determine length. Alpha Actinin- Component of Z Disc - Actin Bundling,
Note Banding Pattern- be familiar. Calcium released by voltage sensitive channels in SR,
allow for all myofibrils to spontaneously contract in muscle cell. Tropomyosin- rod
shaped Actin binding protein blocks myosin binding site. Calcium binding to regulatory
troponin complex, facilitates rearrangement of tropomyosin, now myosin can bind actin.
Absence of Calcium- no contraction. Steps in myosin movement – see slide for details.
Actin based motility in non muscle cells. Cell with ability for whole cell locomotion.
Example: Fibroblast moving toward site of wound. Cell needs to extend. Attach to
surface , and contract back end to make way along. Actin organized in bundles in
Filopodia structures (thin protrusions) and thin sheets in Lamellipodia. Actin
concentration at leading edge- a result of nucleation of actin by ARP proteins. ARP
function as nucleation sites- attach onto + end of Actin filaments, now formation of new
actin filament branch from site. Small Family of Rho G proteins ( monomeric like Ras)
activated in intracellular signaling pathway and target ARP proteins for cytoskeletal
rearrangement.
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