5 Cytoskeleton

1. structural scaffold that determines cell shape & polarity

2. Causes tension & locomotion

3. Organizes & drives intracellular traffic

4. Basis for mitosis & meiosis

• organelle transport is MT dependent

• also function in cell motility & cell division

• they're the LARGEST of the 3 fibers that make up the cell cytoskeleton

an ATPase motor that functions in RETROgrade transport (from synapse → cell body)

• eg. ENDOcytosis & 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 cell body → synapse)

• eg. EXOcytosis & the movement of synaptic transmitter vesicles from the neuron cell body along the axon to the synapse

they make up the basis of the cell’s centrosomes that become spindle fibers (mitotic spindle apparatus) during mitosis

a pair of centrioles surrounded by pericentriolar material that contains a unique tubulin isoform, gamma-tubulin, which nucleates microtubule assembly

microtubules that take part in mitosis by creating the mitotic spindle; present as pairs in the centrosomes of all cells

• specialized microtubule-based HYPERSTABLE structure that makes up the core of cilia & flagella

• contains DYNEIN [retrograde transport] arms

• the 9 + 2 array is the molecular anatomy of the axoneme

they make up cilia & flagella, movement of which is MT-dependent

microtubules that anchor cilia & flagella to the cell

• affected individuals lack or have abnormal Dynein arms normally found in the microtubule axoneme of cilia & flagella

• abnormal or no movement of cilia & flagella

• male infertility, ↑ UTI in females, associated situs inversus of throracic & abdominal viscera, chronic rhinitis, sinusitis, & brochiectasis associated with ciliary/flagellar dyskinesis

am extremely important chemotherapeutic 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 & is therefore commonly used for cancer chemotherapy

binds MT subunits & prevents their polymerization

used to treat gout & cancer

class of anti-cancer drugs including vincristine & vinblastine; binds microtubule subunits & prevents them from polymerizing

[opposite mechanism of Taxol]

stabilize & regulates how fast the microtubules + end is growing

Alzheimer's, Dementia

• result from altered splicing & inability to produce proper Tau proteins

• without Tau proteins microtubules cannot function normally

• without cell transport cells eventually die → severely degraded brains

• 1. give cells shape & aid in:
• 2. muscle contraction
• 3. cytokinesis
• 4. phagocytosis
• 5. platelet aggregation

• smallest of the 3 fibers that make up the cell cytoskeleton

actin-based structures that provide support for endothelial cells (eg. that line large arteries) against the shear forces exerted by flowing blood in high-pressure blood vessels

• α: located in all cells

• β: localized along the migrating front

• γ (gamma)

Myosin

actin pairs with Myosin to generate force in muscle cells

(like dyenin & kinesin, it’s an ATPase)

1. Platelet Aggregation: rearrangement of actin microfilaments → aggregation of platelets (1st step of clotting)

2. Cytokinesis: contractile ring in cell division is an actin based structure

Actin

• eg. Listeria bacteria & Vaccina/Variola viruses hijack cells’ actin machinery & have them protrude from the cell

• these actin “spikes” enter neighboring cells via Phagocytosis → cells merge → spread of infection to other cells

bacteria that hijack microfilaments to rapidly assemble & transport them from cell to cell

• actin “spikes” driven by bacteria protrude from origin cell & either poke into neighboring cell or are phagocytosed by it, spreading the infection

• Vaccina virus causes smallpox

• Listeria causes food poisoning, meningitis & spontaneous abortion

1. Sarcomeres in muscle

2. Microvili in the gut

hyperstable structure FILLED with actin that increase surface area for absorption in intestinal epithelial cells

* the Terminal Web that anchors actin microfilaments in microvilli & is analogous to the Basal Body that anchors axonemes (MTs) in cilia

therefore if it's a drug question the answer is NOT likely to be that they affect microfilaments

• • 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 & are targeted for destruction, leading to ↓ RBC count (anemia) & splenomegaly
• • can be caused by any defect in an anchoring protein of the erythrocyte membrane
• • inherited in an autosomal dominant & recessive fashion

transport protein responsible for mediating exchange of Cl- for HCO3- (bicarbonate) across the plasma membrane that also plays an anchoring role in the RBCs [double duty]

along with Actin, one of the proteins involved with proper RBC plasma membrane formation [relevant to understand Hereditary Spherocytosis]

• a cytoskeletal protein that lines the intracellular side of the plasma membrane in eukaryotic cells

• • 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

• 1. Keratin - epithelia (skin), nails & hair
• 2. GFAP (glial fibrillary acidic protein) - glial cells (astrocytes)
• 3. Neurofilamin- neurons
• 4. Lamin - nuclei of ALL cells
• 5. Vimentin - fibroblasts, endothelial cells (mesenchymal cells)
• 6. Desmin - muscle cells (smooth, striated, cardiac)

King George Never Liked Virgin Daiquiris

Nuclear Lamins

they’re found in ALL cells with a nucleus

*the hyperstable structure of intermediate filaments*

• found in epithelial cells & made of keratin

• provides a lot of attachment force to anchor cells together in tissue

• ~ a spot weld between 2 epithelial cells

how epithelial cells attach to basal lamina

• when cell makes half a desmosome & it anchors via keratin (in skin cells) to the basement membrane

Blistering Disease

• desmosomes are made of keratin, so with nonfunctional keratin, epithelial cells are neither attached to each other or to the basal lamina via hemidesmosomes