Cytoskeleton

Question 1

3 y/o m/c lab with large “cauliflower-like” mass on base of penis
history - owners adopted six weeks before from a rescue, bloody penile discharge intermittently since adoption
Biopsy - large round cells with moderate mitotic acticity and mild anisocytosis and anisokaryosis
Diagnosis?

Answer 1

canine transmissible venereal tumor

Question 2

Cytoskeleton - how are cells organized and what are the categories?

Answer 2

organized and held together by a set of structural proteins that are divided into three categories
microtubules, microfilaments, intermediate filaments

Question 3

What is cytoskeleton important for?

Answer 3

cell shape, motility, strength, processes, polarization, signaling, organelle organization, movement of macromolecules, and membrane organization

Question 4

Microtubule structure

Answer 4

hollow tubes around 24 nm in diameter, often centered around nucleus radiating outward, alpha exposed at negative end while tubulin is exposed at positive end, i guess -/+ are not charges

Question 5

alpha end is more likely to..

Answer 5

regress

Question 6

beta end is more likely to…

Answer 6

grow

Question 7

where are microtubules found?

Answer 7

general cytoplasmic organization, mitotic spindle, axons and dendrites, cilia

Question 8

microtubule functions

Answer 8

cell scaffolding and polarization, polarized movement of organelles, proteins, and dna
Resists compression

Question 9

microtubule transport

What are the two motor proteins and where do they move?

Answer 9

polarized tubules and allow polarized movement. Two motor proteins - kinesin (toward positive end, move something away from the center), dynein (toward negative end, move something toward center). Bind to cargo and “walk” down the tubules

Question 10

microtubule regulation - nucleation
what increases assembly?
What are the two major nucleation sites?
What do the nucleation sites contain?

Answer 10

microtubules are slow to assemble. Introducing a template drastically increases MT assembly. Nucleation sites - centrosomes and basal bodies, both contain gamma-tubulin

Question 11

Microtubule regulation - nucleation
Nucleation polarizes what?
Where are minus ends anchored and where do positive ends grow?

Answer 11

nucleation polarizes microtubule assembly. Minus ends are anchored in the centrosome and positive ends grow toward periphery.

Question 12

what determines polarization of MT?

Answer 12

location and number of centrosomes

Question 13

MT regulation - dynamic instability.
Where do tubulin dimers bond?
What does B-tubulin hydrolyze?
High concentration of GTP dimer do what?
Low concentration of GTP-bound dimers do what?

Answer 13

tubulin dimers must be bound to GTP to bind to the + end of MT
B-tubulin slowly hydrolyzes GTP to GDP
High concentrations of GTP-dimer in solution promote MT growth and stability.
Low concentration of GTP-bound dimers in solution promote MT catastrophe and collapse

Question 14

What does dynamic instability do overall

Answer 14

Uses up energy but allows rapid regulation of MT network

Question 15

What are MAPs and what can they do?

Answer 15

Microtubule associated proteins, can stabilize, destabilize, cause bundling, cause branching of MT structure and cause interaction with other cytoskeleton fibers or cell junctions and can also move protein or organelles along the MAT

Question 16

Microfilament structure

Answer 16

double helical fibers, found throughout the cell but mostly toward periphery, only one subunit, actin assembles into a polarized strand

Question 17

Microfilaments found in..

Answer 17

cell cortex, microvilli and stereo-cilia, lamellipodia, filopodia, and muscle fibers

Question 18

primary functions of microfilaments

Answer 18

cell membrane organization, ameboid movement, muscle contractions, and cytokinesis
Resists stretching

Question 19

What does polarization allow for microfilaments?
What are the MF motor proteins?
Myosin head bind to what and hydrolyzes what?
ATP hydrolysis causes..

Answer 19

polarization allows polarized transport
MF motor proteins are myosins
Myosin head that binds to actin filaments and hydrolyzes ATP
ATP hydrolysis causes a change in shape in the myosin molecule, pushing it along the microfilament.

Question 20

ATP hydrolysis causes what which causes what

Answer 20

causes a change in shape in the myosin molecule, pushing it along the microfilament, this movement is used to move vesicles, protrude membranes, contract the cell

Question 21

muscle fibers are organized how?

Answer 21

specialized and densely organized fibers of actin and myosin

Question 22

What can actin binding proteins do in MF regulation?

Answer 22

stabilize MF, destabilize MF, encourage MF polymerization, cap MF< cause bundling of MF, crosslink MF, Nucleate/cause branching of MF, Bind MF to membrane/ecm, and generate force along MF

Question 23

Different Microfilament regulation ways

Answer 23

Dynamic instability/tread milling, nucleation, and actin binding proteins.

Question 24

what are intermediate filaments made of?

Answer 24

fibrous (non-globular) proteins, the long fibrous proteins bundle and twist together into rope like structures

Question 25

different tissues have different IF proteins in what?

What can we do with this information?

Answer 25

different tissues have different proteins.

Can use this information for cell identification.

Question 26

Cytokeratin is in what type of cells?

Answer 26

epithelial cells

Question 27

In IF structure, different tissues experiences different ___?

Answer 27

forces

skin vs liver

Question 28

What can IF attach to and hold in place?

Which explains why its what kind of network?

Answer 28

organelles

non-motile scaffolding

Question 29

What does IF structure resist and how?

Answer 29

resists shearing, intermediate fibers are able to resist deformation and when they do deform, spring back into position w/o breaking

Question 30

Why would IF need to change?

Answer 30

in response to changing conditions.

Question 31

What do nuclear lamins do?

Answer 31

support the nuclear membrane, phosphorylated by lamin kinases during entry into prophase which destabilize the IF

Question 32

The lamins are dephosphorylated when and what does it allow

Answer 32

on entry to telophase which allows reassembly

Question 33

3 y/o m/c lab with large “cauliflower-like” mass on base of penis
history - owners adopted six weeks before from a rescue, bloody penile discharge intermittently since adoption
Biopsy - large round cells with moderate mitotic acticity and mild anisocytosis and anisokaryosis
Treatment?

Answer 33

MT organization changes drastically during cell cycle and mitosis. Careful MT regulation (both assembly and disassembly) is necessary for proper formation of the mitotic spindle. Substances that disrupt the MT assembly or disassembly will disrupt the mitotic spindle leading to apoptosis. Vincristine binds to MT dimers, preventing MT assembly. Vincristine is a first-line treatment of CTVT since the tumors are going through the cell cycle much more rapidly than healthy cells. (other anti-cancer drugs, like taxol, bind to MT and stabilize them preventing disassembly).