Cytoskeleton: Microtubules Flashcards
three types of cytoskeletal filaments in the cell
microtubules, microfilaments (also know as actin) and intermediate filaments
microtubules
1 of the 3 types of cytoskeletal filaments in the cell, can be thought of as the “bones” of the cell. Function: maintain cell shape, rigidity and structure, as well as transport of cargo and cell division.
alpha and beta tubulin
the two proteins that make a dimer that is the microtubule building block
protofilament
alpha and beta tubulin dimers stack one on top of another in in head to tail orientation to produce this, polarized
13
of protofilaments that assemble into each hollow microtubule
alpha tubulin
the end of a microtubule with exposed ___ ___ is considered the negative (minus) end of the molecule
beta tubulin
the end of a microtubule with exposed ___ _____ is considered the positive (plus) end of the molecule
Gamma tubulin ring complex (or microtubule organizing center [MTOC])
microtubules are nucleated from these sites, which are located in the centrosome (close to the nucleus). These sites function to help alpha and beta tubulin dimers to associate into filaments.
dynamic instability
in order for cells to function properly, microtubules need to be able to change shape, grow (rescue), and shrink (catastrophe). This concept is known as
GTP cap
a growing microtubule has this, which stabilizes the microtubule and allows for continued adding of dimers. When growing slows down or stops, you eventually get a microtubule without this because even the most distal alpha-beta dimers have hydrolyzed GTP
kinesins
motor proteins that move cargo toward the (+) end of the microtubule (beta end), and thus to the periphery of the cell
-when bound to ATP, has increased affinity for microtubule track; when unbound, lower affinity for track
dyneins
motor proteins that move cargo toward the (-) end of the microtubule (alpha end), and thus toward the nucleus/interior of cell. These are much larger, consist of many subunits, and require regulatory complexes for function, which has limited our ability to study them
axonemal dynein
found exclusively within cilia and the flagellum, the microtubules themselves are the cargo - sliding them against each other allows for bending and power stroke
cilia
small finger-like protrusions from cell surfaces, found on epithelial linings to generate waves that move mucous down the respiratory tract, has 9+2 microtubule structure
primary ciliary dyskinesia (PCD)
disease that causes motile cilia to be defective = airway epithelia movement defective, buildup of mucus and increased risk of infection, sperm motility defective, cilia of female reproductive track defective - infertility
primary cilium
non-motile cilium, has 9+0 organization, function in mechanosensation and cell signaling, most cells have 1 on surface.
polycystic kidney disease (PKD)
disorder of primary cilium function that results in kidneys being unable to sense flow, unable to properly filter urine, = kidney failure
Bardet-Biedl syndrome (BBS)
relatively rare disorder of the primary cilium, symptoms of the disease include ocular defects, polydactyly, defective kidney function and weight gain. Some behavioral and cognitive abnormalities are also observed.
Lissencephaly
disorder of microtubule organization that causes cargo buildup on neuronal axons, causing defective transmission of impulses. Symptoms: smooth brain, seizures, muscle spasms, dysphagia, psychomotor retardation. Arises due to mutation or loss of 1 copy of Lis1 which regulates dynein.
dynactin complex
regulator of the dynein motor, helps the dynein motor load onto the tracks. One component of the complex is encoded on Dctn1 - if mutations arise, leads to Perry syndrome or distal spinal and bulbar muscular atrophy
Perry syndrome
autosomal dominant disease resulting from mutations within the microtubule binding region of Dctn1. Symptoms usually present late in life.
Symptoms: tremors, weight loss, depression
Distal spinal and bulbar muscular atrophy
a motor neuron disease caused by mutations in the binding region of Dctn1. Symptoms present earlier than the other disease. Symptoms: muscle weakness, muscle atrophy, motor deficits
vinblastine
drug used in cancer treatment in low doses, destabilizes microtubules thus killing cells undergoing replication
taxol
drug used in cancer treatment in low doses, stabilizes microtubules which causes them to be rigid, cells undergoing mitosis will die