MA4 Cytoskeleton Flashcards
cytoplasm
a dynamic 3D structure that acts as both skeleton and muscle for movement and stability, the cytoskeleton is an essential part of the cytoplasm
Primary fibers of the cytoskeleton (filament types)
microfilaments, microtubules and intermediate filaments; they are polymers of protein subunits and each type is associated with specific filament-associated proteins to form a filament system
Functions of the cytoskeleton
- establish cell shape
- mechanical strength
- locomotion
- chromosome separation (cell division)
- intracellular transport
Microfilaments definition
smallest and most abundant cytoskeleton filaments, and are responsible for movement (gliding, contraction, cytokinesis; causes muscle contraction by associating with myosin)
Microfilament structure
Fine, thread-like protein fibers (7 nm diameter) composed of (helical) ACTIN monomers
microfilaments have polarity; new actin monomers are added to the + end and broken down form the - end (they self assemble w/o energy but require ATP hydrolysis to break down)
Associated with ABPs (actin binding proteins that regulate MF assembly into high order structures)
Actin
a globular protein 43-46 kD MW, which binds to ATP
the most abundant cellular protein
Actin molecules are joined together in a twisted double-strand (helical actin) to form a microfilament
Microfilament cellular localization
Found throughout the cytoplasm w/o a central organizing structure
MFs are concentrated at the cell’s periphery just below the plasma membrane and in microvilli.
They are also found in stress fibers, protrusive structures (filapodia, lamellipodia, ruffles) and in the cleavage furrow during cell division
MF cellular functions
cytoplasmic viscosity (MF & ABP form meshwork) motility (MF interaction w/ myosin = intracellular movement; cellular motility when in ruffling membrane of migrating cells) anchoring cytoplasmic proteins (via ABPs) structural rigidity (bundling of MFs with ABPs - microvilli and sterocilia)
MF Drugs
Cytochalasin (depolymerization)
Phalloidin (stabilization)
Blebbistatin (inhibits non-muscle myosin)
Duchenne Muscular Dystrophy
A MF disease; a mutation in dystrophin (ABP linking actin to plasma membrane) causing muscle cell death. Patients lose voluntary muscles, requiring a wheel chair by teens, often die in early 20s
Cystic Fibrosis
A MF disease; actin interacts with CFTR to change opening and closing of the Cl- channel. Mutant CFTR does not interact with actin
Also a MT disease; thick mucus in the airways of CF patients blocks the motility of cilia in the respiratory epithelium, which would normally clear mucus, dust and bacteria. Without ciliary action, mucus is not removed from the airway and potential for infection is increased
Microtubules definition
MTs are cylindrical tubes (20-25 nm in diameter), the largest elements of the cytoskeleton. They act as scaffolds to determine cell shape and provide tracks for cell organelles/vesicles to move along. MTs form spindle fibers that separate chromosomes in mitosis; when arranged in geometric patterns inside flagella and cilia, they are used for locomotion
MTs provide: structure, polarity, mobility and alignment
MT structure
composed of alpha and beta tubulin that make a heterodimer.
in cross-section, MTs have 13 dimers arranged around a hollow core; a longitudinal section shows rows of dimers called protofilaments
MTs have polarity (new subunits are added to the + end and disassembly occurs from the - end; occur very rapidly in response to Ca2+ and temperature)
Self assembly is possible (energy not required but adding GTP to the ends stabilizes the MT)
MTs are associated with MAPs (microtubule associated proteins) that stabilize the structure
MT cellular localization
MTs radiate from a Microtubule Organizing Center (MTOC) near the nucleus (centrosome - 2 centromeres). The MTOC anchors the - ends, reducing disassembly and the + end extends into the cell
MTs are important in centrioles (cell division), cilia and flagella (locomotion)
MT cellular functions
structural rigidity (scaffolding, can change rapidly)
road map (motor proteins)
cytokinesis (centrioles)
motility
Motor proteins
Move along MTs transporting vesicles in the cell using ATP.
Kinesins are +end directed, meaning they move from the - end to the + end
Dyneins are - end directed, moving from the + end to the - end
- end is the MTOC; + end is the cell periphery
Centriole structure
form the mitotic spindles during cell division
they have 9 triplets arranged in a circle; each triplet consists of 3 microtubules joined together (1 of 13 protofilaments, 2 of 13 protofilaments each)
when the cell is not dividing the centrioles are found as paired structures in the MTOC, lying at right angles to eachother
Cilia and flagella structure
they have 9 doublets with a central pair
at the base of each cilium or flagellum is a basal body which has the same structure as a centriole (9 MT triplets)
They are motile through the action of dynein arms attached to the doublets.
MT Drugs
Taxol: stabilizes MTs, preventing further (dis)assembly; used to treat lung, ovarian, breast cancer
Antitubulins: destabilize MTs (colchicine, vinblastine, podophyllin)
Lissencephaly
“smooth brain,” a MT disease where affected individuals are severely retarded, have intractable seizures, die by age 6. Caused by a genetic defect in dynein motor function, leading to failure in neuronal migration
Polycycstic kidney disease
a MT disease; mutations in 2 proteins normally found in the primary cilium of kidney cells, causing excess proliferation that leads to cyst formation and renal failure
Kartagener’s syndrome
a MT disease; a form of Primary Ciliary Dyskinesia is caused by another dynein mutation. Patients without ciliary function have recurrent respiratory infections and fertility problems. This disorder is associated with situs inversus, suggesting a role of cilia in early development
Alzheimer’s disease
a MT disease; can result from hyperphosphroylation of the tau protein (a MAP) that self-assemble to form tangles
Intermediate filaments definition
IFs are larger than MFs but smaller than MTs (10 nm diameter) There are >50 members of the IF family. They differ in molecular weight and tissue specificity, but all have conserved structural similarities. A cell may have more than 1 type of IF protein. They are the only part of the cytoskeleton not essential for survival but are still considered organelles
