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What are the functions of the cytoskeleton (4)?
- 1. Structural scaffold that determines cell shape & polarity
- 2. Causes tension & locomotion
- 3. Organizes and drive intracellular traffic
- 4. Basis for mitosis & meiosis
function in organelle transport, cell motility & cell division; they're the largest of the 3 fibers (at 24 nm) that make up the cell cytoskeleton
- an ATPase motor that functions in retrograde transport (from the synapse to the cell body)
- • eg. ENDOcytosis and the movement of synaptic vesicles from the synapse along the axon back to the neuron cell body
- • Dynein 'arms' are the motor for many microtubule functions
- an ATPase motor that functions in orthograde transport (from the cell body to the synapse)
- • eg. EXOcytosis and the movement of synaptic transmitter vesicles from the neuron cell body along the axon to the synapse
How do microtubules function in cell motility?
they make up cilia and flagella
What part do microtubules play in cell division?
they make up the basis of the cell’s centromeres that become spindle fibers during mitosis
What are the two subunits of microtubules?
alpha and beta tubulin
What are the accessory proteins of microtubules and what purpose do they serve?
- • MAP: stabilizing & destabilizing microtubules, guiding microtubules towards specific cellular locations, cross-linking microtubules, & mediating interactions of microtubules with other proteins
- • Tau: stabilize and regulates how fast the microtubules + end is growing
- Alzheimer's, Dementia
- • result from altered splicing and inability to produce proper Tau proteins
- • without Tau proteins microtubules cannot function normally
- • without cell transport cells eventually die --> severely degraded brains
microtubule structure that makes up the core of cilia and flagella (contains DYNEIN [retrograde transport] arms)
Kartagener’s Syndrome (clinical vignette)
- affected individuals have dyskinesis because they lack or have abnormal dynein arms normally found in the microtubule axoneme of cilia & flagella
- • abnormal or no movement of cilia and flagella
- • male infertility, associated situs inversus of throracic & abdominal viscera, chronic rhinitis, sinusitis, and brochiectasis associated with ciliary/flagellar dyskinesis
microtubules that take part in mitosis by creating the mitotic spindle; present as pairs in the centrosomes of all cells
microtubules that anchor cilia and flagella to the cell (centrioles that nucleate microtubules in axonemes)
a pair of centrioles surrounded by pericentriolar material that contains a unique tubulin isoform, gamma-tubulin, which nucleates microtubule assembly
a drug that freezes microtubule polymers so once formed they can't disassemble; this makes it impossible for them to function in things like cell division or organelle transport; it blocks mitosis, and is therefore commonly used for cancer chemotherapy
used to treat gout and cancer; binds subunits and prevents their polymerization
class of anti-cancer drugs including vincristine and vinblastine; binds microtubule subunits and prevents them from polymerizing
Microfilaments (5 functions)
- 1) give cells shape, and aid in
- 2) muscle contraction
- 3) cytokinesis
- 4) phagocytosis
- 5) platelet aggregation
- • they're the smallest of the 3 fibers (at 7 nm) that make up the cell cytoskeleton
provide support for endothelial cells (eg. that line large arteries) against the shear forces exerted by flowing blood in high-pressure blood vessels
What are the three isoforms of actin?
- • alpha: located in all cells
- • beta: localized along the migrating front
- • gamma
What are the Hyperstable actin (microfilament) structures?
- 1) Sarcomeres in muscle
- 2) Microvili in the gut
- increase surface area for absorption; actin modulated extensions
- terminal web anchor actin microfilaments in microvilli are analogous to basal body in cilia
You do not need to know the drugs that affect actin because they're too toxic for human use
therefore if it's a drug question the answer is NOT likely to be that they affect microfilaments
______ pairs with myosin in muscle molecules to generate force
cytokinesis, platelet aggregation are ______ based process
Listeriosis & Vaccina Viruses
- bacteria that hijack microfilaments to rapidly assemble and transport them from cell to cell; actin “spikes” driven by bacteria protrude from origin cell and either poke into neighboring cell or are phagocytosed by it, spreading the infection
- • Vaccina virus causes smallpox
- • Listeria causes food poisoning, meningitis & spontaneous abortion
- • a family of genetic diseases where actin is mutated
- • actin is involved in the structure of RBCs therefore in this disease RBCs cannot get small enough to pass through tiny blood vessels in the spleen
- • inflexible RBCs get trapped in spleen and are targeted for destruction, leading to decreased RBC count (anemia) and splenomegaly
- • inherited in an autosomal dominant and recessive fashion
- • provide mechanical & structural integrity for cells
- • involved in cell-cell contact & communication
- • do NOT have any associated proteins nor do they bind ATP or GTP
What are the six classes of intermediate filaments and where are they expressed?
- 1) Keratins - epithelia (skin), nails & hair
- 2) GFAPs (glial fibrillary acidic protein) - glia
- 3) Neurofilaments - neurons
- 4) Lamins - nuclei of cells
- 5) Vimentins - fibroblasts
- 6) Desmin - skeletal, cardiac, & smooth muscle
- King George Never Liked Virgin Daiquiris
What type of intermediate filaments are not cell-type specific?
nuclear laminas; found in all cells with a nucleus
Desmosome (cytoplasmic plaques)
found in epithelial cells made of keratin; spot weld between two epithelial cells provides a lot of attachment force to keep cells together in tissue; are hyperstable intermediate filaments
how epithelial cells attach to basal lamina; when cell makes half a desmosome and it attaches to the base aka the basal lamina
What happens when you have defective keratins?
A blistering disease, because desmosomes (junctions that attach cells to each other) are made of keratin, so with nonfunctional keratin, the epithelial cells are neither attached to each other or to the basal lamina via hemidesmosomes
cytoskeletal protein that lines the intracellular side of the plasma membrane in eukaryotic cells (along with actin one of the proteins involved with proper RBC plasma membrane formation; relevant to understand Hereditary Spherocytosis)
membrane-spanning protein in the RBC that transports sugar molecules
Band 3 Protein
transport protein responsible for mediating exchange of Cl- for HCO3- (bicarbonate) across the plasma membrane
A patient presents with a muscle disease associated with a deletion mutation in the myosin gene product. Would a muscle biopsy need to be performed in order to characterize the mRNA produced?
Yes, because transcription from DNA to mRNA is cell type-specific
This process is the first step following dephosphorylation of an intermediate filament protein by a phosphatase:
Understanding the function(s) of which of the choices is most likely to inform us about the aging process, particularly in the cardiovascular system?
Lamin A (Progeria)
You see a 20-year-old female in clinic with multiple café au lait spots, axillary freckling and cutaneous neurofibromas, all present in the left upper quadrant only. The remainder of the physical exam is negative and family history is unremarkable. You suspect a form of neurofibromatosis. What is the most likely explanation for these findings?