cytoskeleton Flashcards
cytoskeleton
dynamic intracellular structure, establishes order in cell, organizes cell in environment. Provides cell shape, mechanical strength, locomotion, support of plasma membrane, scaffold for organelles, intracellular transport.
3 cytoskeletal elements
microfilaments, microtubules, and intermediate filaments
microtubule
alpha/beta tubulin dimer, tubular structure 25nm in diameter, used for movement (flagella, cilia), cell organization, movement of organelles, cell division.
intermediate filament
complex rope, 10nm diameter, made of vimentin, keratin, and neurofilaments, used for mechanical stability. Have head and tail on either side with coiled coil ligament in the middle. Overlap to form final form. Cell dies without them.
cytoskeletal dynamics of MTs
microtubles contantly in grow in the - to + direction. GTP cap stabilizes, when it breaks the whole thing falls apart. Tail is also important to stability, acetulation protects it from enzyme degredation.
drugs and tubulin
Colchicine, Vinblastine, and vincristine inhibit MT polymerization. Paclitaxel binds MT and stbilizes them causing tubule and tubulin aggregates. All block mitosis
molecular motor on MTs
organelles (vesicles and mitochondria) travel using MTs as tracks. Do so in conjunction with proteins that hydrolyze ATP and turn the energy into motion. Contain cargo-binding domain and a “head” region that hydrolyzes ATP and reversibly binds to MT.
Mechanochemical cycle MTs
motors: bind to MT (bound to ATP), confirmational change, MT release(bound to ADP), confirmation relaxation, binds MT, etc. each step is ~60nm
2 classes of MT motors
kinesins (move cargo to plus end) and dyneins (move cargo to minus end)
microtubules in mitosis
mitotic spindles made from MT. segregate the replicated chromosomes. Astral MTs radiate out of centrosome, kinetochore MTs attached to kinetochore formed at centromere of duplicated chromosomes, Overlap MTs interdigitate at the equator of the spindle.
chromosome seperation
motors and overlap MTs cause spindle growth and centrosomes become mroe distant, enhanced by astral MTs. Minus end motors with shortening kinetochore MT shortening separate daughter chromosomes and moce them along MT to centrosome
cytoskeleton and disease
neuropathies come from problems with microtubules or motors in axonal transports. Other diseases (like huntingtons) can be further problematic with a transport disorder. K8 and K18 mutations cause liver disease. Keratin expression used for diagnosis and prognostic marker for cancer. Lamanin mutations cause problems wtih lack of lipid storage and premature aging.
cytoskeletal dynamics of actin filaments
key steps, nucleation and extension/retraction. When actin is bound to ATP it forms filaments, when it is bound to ADP it does not. Most as monomer bound to ADP. Minus end has ATP cleft exposed. Grows from - to + and - ends depolymerizes. Both ends can grow to some extent.
nucleation
take 3 monomers together to form nucleation center. Once nucleation center forms filament grows. 2 groups of proteins nucleate actin. Arp2/3 forms branches of actin. Formen mimics actin and binds 2 actin to form nucleation center and filaments form. Formen activated by small monomeric GTPases. (Rac and Row)
actin and epithelial cell polarity
microvilli are packed with actin. That attach to the terminal web (also made of actin).