MA4 Cytoskeleton Flashcards

1
Q

cytoplasm

A

a dynamic 3D structure that acts as both skeleton and muscle for movement and stability, the cytoskeleton is an essential part of the cytoplasm

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2
Q

Primary fibers of the cytoskeleton (filament types)

A

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

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3
Q

Functions of the cytoskeleton

A
  1. establish cell shape
  2. mechanical strength
  3. locomotion
  4. chromosome separation (cell division)
  5. intracellular transport
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4
Q

Microfilaments definition

A

smallest and most abundant cytoskeleton filaments, and are responsible for movement (gliding, contraction, cytokinesis; causes muscle contraction by associating with myosin)

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5
Q

Microfilament structure

A

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)

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6
Q

Actin

A

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

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7
Q

Microfilament cellular localization

A

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

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8
Q

MF cellular functions

A
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)
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9
Q

MF Drugs

A

Cytochalasin (depolymerization)
Phalloidin (stabilization)
Blebbistatin (inhibits non-muscle myosin)

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10
Q

Duchenne Muscular Dystrophy

A

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

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11
Q

Cystic Fibrosis

A

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

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12
Q

Microtubules definition

A

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

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13
Q

MT structure

A

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

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14
Q

MT cellular localization

A

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)

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15
Q

MT cellular functions

A

structural rigidity (scaffolding, can change rapidly)
road map (motor proteins)
cytokinesis (centrioles)
motility

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16
Q

Motor proteins

A

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

17
Q

Centriole structure

A

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

18
Q

Cilia and flagella structure

A

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.

19
Q

MT Drugs

A

Taxol: stabilizes MTs, preventing further (dis)assembly; used to treat lung, ovarian, breast cancer
Antitubulins: destabilize MTs (colchicine, vinblastine, podophyllin)

20
Q

Lissencephaly

A

“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

21
Q

Polycycstic kidney disease

A

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

22
Q

Kartagener’s syndrome

A

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

23
Q

Alzheimer’s disease

A

a MT disease; can result from hyperphosphroylation of the tau protein (a MAP) that self-assemble to form tangles

24
Q

Intermediate filaments definition

A

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

25
Q

IF structure

A

IF proteins join together as a coiled-coil homodimer
2 dimers combine to form tetramers, which align to form protofilaments
8 protofilaments combine to form 1 intermediate filament
IF proteins are almost always polymerized and are difficult to disassemble.

26
Q

IF cellular localization

A

IFs are found throughout the cytoplasm and in the nucleus

they are concentrated in a basket around the nucleus, and at desmosomes

27
Q

Nuclear IFs

A

component polypeptides: lamins A, B, C

location: nuclear lamina (inner lining of nuclear envelope)

28
Q

Vimentin-like IFs

A

component polypeptide: vimentin; desmin; glial fibrillary acidic protein
location: many cells of mesenchymal origin; muscle; glial cells

29
Q

Epithelial IFs

A

component polypeptides: type 1 keratins (acidic) and type 2 keratins (basic
location: epithelial cells and their derivatives (i.e. hair and nails)

30
Q

Axonal IFs

A

Component polypeptides: neurofilament proteins

location: neurons

31
Q

IF cellular functions

A

Structural strength
Space fillers (axons -> conduction velocity)
Keratins (IFs in epithelial cells - strength, dx of carcinomas)
Lamins (IFs in nucleus)
Vimentin (many cells; flexibility and resilience under stress; anchors organelles)

32
Q

Cell Division - depolymerization

A

Before cytokinesis, MTs must depolarize to allow the cell to become spherical and provide subunits to form the spindle apparatus
Centrioles also replicate in the centrosome (MTOC); the centrosome splits and 2 halves move to opposite sides of the cell

33
Q

Cell Division - Aster formation

A

Spindle MTs extend from each aster (+ ends outward)
Motor proteins push against the spindle MTs of the opposite aster to separate the asters
Other spindle MTs attach to the plasma membrane and are pulled towards the cell periphery

34
Q

Cell Division - Formation of kinetochore MTs

A

Kinetochore microtubules capture sister chromatids by attaching the + end at the kinetochore.
Motor proteins push against the spindle of the opposite aster to separate the asters

35
Q

Cell Division - Cleavage and repolymerization

A

Actin MFs are necessary for cleavage. They form a band at the cleavage furrow btwn daughter cells and w/ myosin the ring contracts, splitting the 2 cells
After cleavage, the aster breaks down and cytoplasmic MTs reform in preparation for differentiation