Intracellular Architecture- Lecture 37 Flashcards

1
Q

What kinds of fillaments compose the cytoskeleton?

A

actin/microfilaments (smallest)
intermediate filaments
microtubules

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2
Q

Describe IF assembly.

A

monomers (elongated, alpha helical with a globular N-terminus and C-terminal tail) combine to form dimers (coiled coil) which associate to form tetramer which associate with 7 other tetramers to form ropelike filaments

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3
Q

What is the function of intermediate filaments?

A

maintaining structure of the cell

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4
Q

What are the families of IF?

A

keratins
vimentins (desmins/fermentins)
nucleofilaments
nuclear lamins

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5
Q

Provide an example of mutation affecting one of the families of IF.

A

epidermolysis bullosa simplex (mutation in keratin 14 adn 5) leads to blistering of skin as a function of mechanical stress

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6
Q

What is the function of microtubules?

A

intracellular organization and transport

form mitotic spindle

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7
Q

Describe the structure of microtubules.

A

grow from a tubulin dimer (one alpha and one beta, each bound to GTP) forming linear protofilament that grow out of centrosomes from minus end (which binds to structures composed of alpha tubulin)

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8
Q

Describe the dynamic nature of microtubules.

A

dimers form linear protofilaments with beta subunit facing outward (intrinsic polarity which directs the association to the plus end), 13 of which combine to form a circular, stiff, hollow tube, as more subunits are added linearly, the inner beta subunits are hydrolized from GTP to GDP for stabilization

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9
Q

How are microtubules used in mitosis?

A

MT grows out of a centrosome (microtubule organizing center) during interphase and become spindle pole bodies

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10
Q

Microtubules grow and shrink in _____.

A

dynamic instability

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11
Q

When are microtubules destabilized?

A

when GTP becomes hydrolized before new dimers bind

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12
Q

Microtubules form _____ which can be used for _____.

A

tracks

transport of organelles from one end of a neuron to the other.

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13
Q

What are the kinds of motor proteins that do the work on microtubules?

A

kinesin (plus end directed motors) or dynein (minus end directed motors)

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14
Q

Describe the structure and movement of motor proteins across microtubule structures.

A

one domain binds the microtubules while the other binds cargo
microtubule binding ends have two heads that move processively to bind and release from microtubules in a walking motion

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15
Q

What kinds of movement are possible across microtubules?

A

anterograde- towards plus end (movement by kinesin- as in synaptic vesicles and axonal growth materials)
retrograde- towards the minus end (movement by dynein- as in recycling of membranes to lysosome in cell body)

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16
Q

What are cilia?

A

abundant projections from epithelial cells that move fluids along a surface in a wave-like fashion

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17
Q

What are flagella?

A

singular, larger projections that are used to propel a cell forward (eg. sperm)

18
Q

The beating motion of cilia and flagella is dependent on _____.

A

specific arrangement of microtubules and the actions of kinesin and dyenin motor proteins

19
Q

____ induce slide of one microtubule against another microtubule in experimerns, however the _____ produces bending in azoneme.

A

Dyneins

linker proteins

20
Q

What are primary cilia?

A

sensory organs (contain receptors for smell as well as photoreceptors for light in rods and cones)
non-motile (because they lack central pair of MTs)
derived from centrioles left over after duplication
usually one per cell

21
Q

Provide an example of a disease resulting from a mutation resulting in loss of cilia function.

A

Polycystic kidney disease

22
Q

What are the different phases of the cell cycle?

A

G1, S, G2, M, and cytokinesis

23
Q

Describe the progression of cell division through the phases of cell cycle.

A

DNA replication —> chromosome condensation and separation (occurring during mitosis) –> separation of chromosomes into two daughter cells (via cytokinesis)

24
Q

During the phases of cell cycling, microtubules existing in the interphase cell become reorganized into _____ which is attached to the ____ which derive from the _____ by duplication.

A

mitotic spindle
centrioles
centrosome

25
Q

What are the three kinds of microtubules in the spindle?

A

kinetochore (bind directly to chromosomes at the centromeres)
overlap/polar (bind to each other overlapping fashion)
astral microtubules (bind to the cell surface)

26
Q

Describe the mechanism by which microtubules facilitate mitosis.

A

MTs are shrtened by dissasembly at both kinetochore and spindle ends
chromosomes are separated via motor proteins pushing and pulling the spindle to move the poles further apart and dynamic instability used to constantly shrink the kinetochore microtubules

27
Q

What is actin?

A

a monomer protein that polymerizes to form actin filaments (microfilaments)

28
Q

What is the function of actin?

A

form structural components of microvilli
found around the cell in cell cortex
form structural belt around cells (adherins)
form structures used to promote cell movement (eg. lamellipodia or filipodia)
promote endocytosis
form part of contractile ring in cell division

29
Q

Describe the structure of actin.

A

ATP bound proteins that polymerize into filaments with a helical arrangement
have polarity and add preferentially to the G-actin end (plus) with nucleotide facing minus end

30
Q

Explain the process of actin filament formation.

A

nucleation
elongation
steady state
these can occur at equal rates on plus and minus ends to produce a treadmilling action
once bound to plus end, ATP hydrolizes (filament contains mostly ADP) which has a weaker affinity for being in a filament and dissociates from minus end

31
Q

Provide examples of proteins that change actin filament stability.

A

CapZ stabilizes actin filaments (found in muscle fibers)
formins stimulate growth (found in stress fibers formed during cell movement)
Arp2/3 stimulates filament branching (occurs at leading edge of cells that are crawling)

32
Q

Describe the process of cell movement/crawling via actin.

A

cells attach to surfaces at local sites (focal adhesions) via integrins that bind to actin
once attached, cell is pushed forward via contractile bundles of actin in association with myosin (motor protein ) in the direction indicated by the leading edge (contain lamellipodium or filopodium)

33
Q

Provide an example of a non-human cell that uses human actin.

A

Lysteria monocytogenes (bacteria) hijacks actin machinery via ActaA, which recriuts actin and machinery that promotes actin branching and assembly resulting in comet tail that “shoots” the bacteria around

34
Q

Explain how actin can be controlled by cell signaling.

A

growth factors bind G-protein receptors which lead to actions of related small GTP binding proteins:
Rac (establishes leading edge)
Rho (stimulates movement via contractions)
Cdc42 (establishes cell polarity and direction of movement)

35
Q

How is skeletal muscle formed?

A

fusion of muscle cells to form myofibril (many repeating sarcomeres)

36
Q

What are sarcomeres?

A

resting muscle that can contract and shorten by 70%

37
Q

What kinds of filaments do sarcomeres have and how are they arranged?

A

thick (correspond to a polymerized form of the motor protein, myosin II)
thin (comprised of actin and actin binding proteins)
arranged with plus ends associated with Z-disks

38
Q

How do muscle cells contract?

A

action potential at neuromuscular junction –> release of CA2+ stores from sarcoplasmic reticulum
myosin II is arranged in a bipolar orientation with head groups on each half having opposite orientations, enabling motor heads to grab onto actin and slide it towards the center of sarcomere
non-processive
each only binds and releases once per cycle

39
Q

Provide examples of drugs that are used to modify microtubules.

A

taxon- inhibits deconstruction

colchicine- inhibits assembly (gout)

40
Q

Provide examples of drugs that are used to modify actin.

A

cytochalasin- inhibits assembly