Cytoskeleton I Flashcards
Name three microtubule severing proteins.
- katanin
- spastin
- fidgetin
Microtubules typically have one end attached to __________
a centrosome or perinuclear microtubule organizing center (MTOC)
- only one in mammalian cells
What are the building blocks of microtubules?
- heterodimers of the protein tubulin (alpha and beta)
- GTP bound to both tubulins
- GTP bound to beta tubulin can be hydrolyzed and is exchangeable
- GTP bound to alpha tubulin cannot be hydrolyzed (trapped)
What is the structure in regards to alpha and beta tubulins to form microtubules?
- alternating alpha and beta subunits create parallel protofilaments
- laterally, interactions are mostly alpha-alpha and beta-beta
Why do microtubules have polarity?
Because one end has an alpha tubulin and the other has beta (due to the dimers)
Why is the plus end the one that grows?
GTP bearing beta subunits favor polymerization
Why does the minus-end tend to disassemble?
As dimers are incorporated more deeply into the microtubule, GTP is hydrolyzed to GDP, which weakens the tubulin interactions in the protofilament
What happens if a microtubule loses its GTP-rich cap?
- rapid shrinkage from the plus-end until GTP containing dimers are added back
- called dynamic instability
What do microtubule capping proteins do?
- bind to the ends of the microtubules
- increase stability
What do microtubule severing proteins do?
- increase microtubule instability by exposing GDP rich parts of the microtubules
- e.g. spastin and katanin
How does Paclitaxel work?
- binds to microtubules and stabilizes them
- causes tubule and tubulin aggregates
Microtubules act as a __________ for organelle positioning.
scaffold (e.g. ER and Golgi are anchored to microtubules)
How do microtubules assist with intracellular transport?
- acts as the tracks for microtubule motor proteins (head domain and cargo carrying domain)
- coordinated with ATP hydrolysis, motor goes through a mechanochemical cycle of binding, conformational change, release, conformational relaxation, re-binding
Which direction do kinesins move cargo?
toward the plus-end of the microtubule
Which direction do dyeins move cargo?
toward the minus-end of the microtubule
What is the mitotic spindle constructed from?
Microtubules
What are astral microtubules?
- contribute to the mitotic spindle
- radiate out form the centrosome
What are kinetochore microtubules?
- contribute to the mitotic spindle
- attached to the kinetochore formed a the centromere of each duplicated chromosome
What are overlap microtubules?
- contribute to the mitotic spindle
- interdigitate at the equator of the spindle
Which direction does the plus end point in relation to the centrosome?
away
What helps cause the centrosomes to grow apart during mitosis?
- plus-end directed, kinesin-like motor proteins bind to overlapping microtubules from opposite poles
- these motors and the elongation of the overlapping microtubules cause the spindle to grow
What is flagella?
- have micro tubular core
- propel sperm
What are cilia?
- have micro tubular core
- occur in large numbers on the apical surface of epithelial cells
- move fluids over the surfaces of cells
What are intermediate filaments?
- fibrous structures of about 10nm
- prominent in cells exposed to mechanical stress
- provide intracellular mechanical support
What are the two categories of intermediate filaments?
- cytoplasmic IFs
- nuclear lamins
Are there cell specific cytoplasmic intermediate filament proteins?
Yes
- keratins
- vimentins
- neurofilament
What do nuclear lamins do?
- filamentous proteins that form a stabilizing meshwork lining the inner membrane of nuclear envelope to provide anchorage for chromosomes and nuclear pores
How are intermediate filaments formed?
- elongated molecules with extended central alpha helical domains that form a parallel coiled coil with another monomer
- form staggered tetramers in anti-parallel fashion
- not polarized
- tetramers assemble into protofilaments
Where are intermediate filaments often anchored?
intercellular junctions
How do keratin mutations result in epidermolysis bullosa simplex?
- interfere with filament assembly
- results in epidermis that is highly sensitive to mechanical stress and blisters easily
How do mutations in the light chain of neurofilaments result in Charcot-Marie-Tooth syndrome?
may interfere with axonal transport of neurofilament subunits and cause peripheral neuropathy
How do mutations in lamins result in various progeria syndromes?
can result in nuclear instability
