Ch. 18 Cytoskeleton Ii: Microtubules And Intermediate Filaments

Front 1

Microtubules play a role in _cellular movement during the interphase and mitosis. the movement is largely due to _ and _ motor proteins. In addition to the functions listed, MTs also cause movement of _ and _.

Back 1

intra
kinesin, dynein
cilia, flagella

Front 2

Cytoskeletal components and functions:
(_), _ _ - organizaing cell polarity
_ _- chromosomes movements MT assembly
_ _- + end-directed vesicle and chromosome transport
_ _- - end-directed vesicles and transport spindle assembly

Back 2

MTOC, spindle pole
microtubule dynamics
kinesin motors
dynein motors

Front 3

Cytoskeleton systems: Microfilaments:
_ binds ATP, form rigid gels, _, and linear _. There is regulated assembly from a large number of locations so they are highly _, _, tracks for _, and the contractile machinery and network at the cell _.

Back 3

Actin
networks, bundles
dynamic
polarized
myosins
cortex

Front 4

Cytoskeleton systems: Microtubules: _-_ _ bind to GTP and are rigid and not easy to bend. They are regulated assembly from a small number of locations, and highly _, _, make tracks for _ and _; and control the organization and long-range transport of _.

Back 4

alpha-beta tubulin
dynamic
polarized
kinesins and dyneins
organelles

Front 5

Cytoskeleton systems: Intermediate filaments: _ subunits don't bind a nucleotide. They have great _ strength and are assembled into pre-existing filaments. They are less _, _, have no _, and are used for cell and tissue integrity

Back 5

IF
tensile
dynamic
unpolarized
motors

Front 6

_ _ subunits compose the wall of a microtubule. alpha tubulin-GTP (-) is irreversible binding but _-_ can block exchange, The beta-tubulin-GDP (+) can exchange for _. fig 18.3 dimers of alpha-tubulin and beta-tubulin form _ which combined the structure is _.

Back 6

heterodimeric tubulin
beta-tubulin
GTP
protofilaments
stiff

Front 7

Arrangement of protofilaments in _, _ , or _ microtubles. They are packed side-by-side to form the wall of the MT. fig 18.4

Back 7

singlet, doublet, or triplet

Front 8

Microtubules are assembled from _ _ _ (_). The polar end is on the _ end and the growth occurs on _ end. fig 18.5

Back 8

mictrotubule organizing centers (MTOCs)
-
+

Front 9

The _-_ _ _ (_) nucleates polymerization of tubulin subunits. MTOCs have high conc of proteins necessary for initiating assembly of MTs. This includes the _ that is thought to nucleate assembly of protofibrils into sheets and tubes via contacts with _-_. fig 18.7

Back 9

gamma-tubulin ring complex (y-TuRC)
(y-TuRC)
alpha-tubulin

Front 10

A centrosome is a (_) and has a triplet structure. fig 18.6

Back 10

MTOC

Front 11

Microtubule assembly and treadmilling: MTs have structural and functional _. Growth occurs at + end because it has a lower _. Beta-tubulin-_ is hydrolyzed to beta-tubulin-_ in the MT interior

Back 11

polarity
Cc
GTP
GDP

Front 12

Microtubule assembly and treadmilling: bc growth occurs at + end, dimer treadmills from _ end to _ end. fig 18.8

Back 12

+
-

Front 13

dynamic instability is an _ property of MTs as they rapidly grow and shrink independently. _ is faster than assembly. fig 18.10

Back 13

intrinsic
disassembly

Front 14

The ends of the growing and shortening MTs appear different. fig 18.12 Growing ends are _ and _ attach here. shortening ends are _, and this splaying probably promotes diassembly. It is explain by GTP cap model.

Back 14

smooth
protofilaments
frayed

Front 15

GTP cap model has been made to explain dynamic instability: beta-tubulin-_ disassembles faster than beta-tubulin-_.Mts with cap seem to grow and those lacking will fall apart.

Back 15

GDP
GTP

Front 16

MT-associated proteins (_) modulate MT behavior. _, _, and _ are regulated by these. MT spacing depends on length of side-binding MT-stabilizing MAP "_ _" arms. Certain drugs affect this like _/_ which blocks MT dynamics at metaphase and also depolmerizes MTs; _ which stabilizes MTs, is used as _-_ drug. blocking MT dynamics can prevetnt passin through the _ _. fig 18.14

Back 16

MAPs
assembly, disassembly, and association
projection domain
anti-cancer
cell cylcle

Front 17

MT-associated proteins (MAPs) modulate MT behavior. some MAPs destabilize MTs by severing them using _ or by binding MT frayed ends or tubulin dimers. Many MAPs are negatively regulated by _. fig 18.16

Back 17

ATP
phosphorylation

Front 18

Different proteins are transported at different rates along axons: classic _-_ experiment showed MT-dependent axonal transport. Axon slices are subjected to _-_ to identify radiolabeled proteins.

Back 18

pluse-chase
SDS-PAGE

Front 19

Different proteins are transported at different rates along axons: (3)
1_ tranport fastest.
2_ have intermediate rates
3_ and _ (IF) subunits are the slowest

Back 19

vesicle
organelles
tubulin and neurofilament

Front 20

Transport goes both directions along MTs in axons: _-goes down the cell body to axon and _ goes via synaptic terminals to the cell body.Vesicles can be transported both directions along same MT and can pass each other.

Back 20

anterograde
retrograde

Front 21

Motor proteins are at both + and - ends but _ only has + ended directed myosin motors. fig 18.18

Back 21

actin

Front 22

The structure of the kinesin microtubule motor protein:
Head binds MT and _.
Linker converts _ _ into movement.
Stalk dimerizes??
Tail has _ _ binding which has cargo binding. fig 18.19

Back 22

ATP
ATP hydrolysis
light chain

Front 23

Kinesin is a _ end-directed motor that goes toward + end and away from MTOC. There are cytosolic kinesins and mitotic kinesins and some mitotic ones are - end directed motors.

Back 23

+

Front 24

Structure and function of select kinesin family members: fig 18.21
Kinesin-#_ and Kinesin-#_ for organelle transport. Kinesin-#_ is bipolar and used in mitosis. Kinesin-#_ is for end assembly.

Back 24

1/2
5
13

Front 25

Kinesin is:
_ end directed motor
head binds to _
neck is _.
bind _s
used in _ process
for _ and _ transport

Back 25

+
ATP
flexible
MTs
mitosis
vesicle and organelle

Front 26

Myosin:
_ end directed motor
head binds to _
neck is _
bind the _s
used in _ and for _ and _ transport

Back 26

+
ATP
rigid
MFs
sytokinesis
vesicle and organelle

Front 27

_ are - end directed motors for retrograde transport.

Back 27

Dyneins

Front 28

Dynein MT motor proteins: completely different structure: _/_ complexes are huge and much dif in structure and organization than kinesins and myosins

Back 28

dynein/dynactin

Front 29

Dynein MT motor proteins: completely different structure:
_- heavy, intermediate and light chain subunits fig 18.24
_- glued: binds dynein and MTS, _ holds 2 halves of dynactin together, _ _ _ (_) binds cargo and dynamtin. fig 18.26

Back 29

dynein
dynactin
dynamitin
Arp1

Front 30

Dynein on a MT: _ _ drives movement by changing the orientation of the head relative to the stem, causing movement toward + end

Back 30

ATP hydrolysis

Front 31

Organelle transport by MT motors: switching bn cystolic _ and _ will reverse cargo transport direction. fig 18.27

Back 31

kinesins
dyneins

Front 32

Multiple motor proteins can move the same cargo: motor of dif types can be on the same cargo: There can be coorperation bn _ and _ motors. e.g. moving from cell body (MT-rich) to the cell cortex (MF-rich) -> cooperation bn _ and _ at the cell cortex.

Back 32

MT and MF
myosin and kinesin

Front 33

All eukaryotic cilia and flagella contain bundles of _ _ _ studded with axonemal _. fig 18.29 the _ arms slide the outer doublet MTs to generate axonemal _ in which axonemal dynein anchored on the A-tubule pulls on the B-tubule ( goes toward _ end) fig 18.31

Back 33

doublet MTs
dyneins
beating
-

Front 34

Cilia and flagella emanate from _ bodies with _ MTs. _ _ moves material up and down cilia and flagella. fig 18.29 and 18.32

Back 34

basal
triplet
Intraflagellar transport

Front 35

The stages of mitosis and cytokinesis in an animal cell: MT _ play a key role in segregating chromosome. fig 18.34

Back 35

dynamics

Front 36

The stages of mitosis and cytokinesis in an animal cell: Metaphase: There are 3 classes of MTs: (3) MT dynamics increase dramatically during _. fig 18.36

Back 36

Kinetochore MT
Astral MT
Polar MT
mitosis

Front 37

The _ is a specialized MT attachment site at the chromosome centromere. MT _ end interact with kinetochore proteins to capture and help transport _.

Back 37

+
chromosomes

Front 38

The kinetochore is a specialized MT attachment sit at the chromosome centromere: The proteins interact with _ _ of the centromere and include _ _ proteins. The kinetochore is the only site of attachement bn _ and _. fig 18.39

Back 38

repetitive DNA
MT motor
MTs and chromosomes

Front 39

Duplicated centrosomes align and begin separating in _. Replication begins in late _ phase and is complete by _ phase, but migration to opposite sides of the nucleus does not occur until _. fig 18.35

Back 39

G1
G2
prophase

Front 40

Organization of the spindle poles orients the assembly of the _ _; the kinetochore capture sets the stage for _.

Back 40

mitotic apparatus
metaphase

Front 41

Mitotic motor proteins (_ and _) and increased _ instability of MTs play key roles in forming the metaphase mitotic spindle. Tension from both poles via _ MTs aligns chromosomes at the metaphase plate. fig 18.40

Back 41

kinesins and dyeins
kintechore

Front 42

Anaphase A: Kinetochore MT _ occurs as chromosome _. MTs shorten at _ end by kinetochore-assoc kinesin and MTs shorten at _ end by spindle pole-assoc kinesin. In total MTs stay _ to kinetochore. fig 18.41

Back 42

shortening
separate
+
-
attached

Front 43

Anaphase B: Poles move apart due to combined action of _ walks along polar MTs towards + ends (pushing poles apart) and _ at PM pulls on poles. Polar MTs elongate so pushing can go further. fig 18.41

Back 43

kinesins and dyneins

Front 44

Cytokinesis is caused by a _ _ of actin and myosin II. The region of _ MT overlap (sand dollar) or _ MT overlap (vertebrate) bn the two spindles delivers or activates contractile ring _. Following second cleavage the _ MT overlaps. Spindle MTs determine _ _. Contractile ring regulation involves inhibitory and activating _ of a myosin light chain

Back 44

contractile ring
astral
spindle
regulators
astral
cleavage plane
phosphorylation

Front 45

Plant cells have many MTOCs: parallel arrays of cortical MTs direct _ _, which in turn determines the direction of cell _. In mitosis, MTs reorganize intos a _ _ around the nucleus where spindle is similar to that in an animal cell but has no _.

Back 45

cellulose deposition
expansion
cortical bundle
centromeres

Front 46

Plant cells have many MTOCs: Cell division involves _ _ formation (cell plate) rather than a _ _ (golgi derived). MT network at cell ends remains intact. fig 18.43

Back 46

cell wall
contractile ring

Front 47

Intermediate filaments: Functions and structure distinguish them from other in cytoskeleton. 10nm in diameter.
Structural- no association with _ _, do not drive cell movement.
Stable- don't easily _.
They don't bind _ (vs MFs: ATP/ADP AND MTs: GTP/GDP). Usually associated with _ _, also often parallel MTs

Back 47

motor proteins
depolymerize
nucleotides
cell membranes

Front 48

Many IF proteins are cell-type specific and others are ubiquitous: These are useful for indentifying the tissue of origin of metastasized tumors.
Class I and Class II- acidic and basic _ in epethelial cells for tissue _ and _. e.g. desmosomes
Class III- _, _, and _ in muscle, glial cells, and mesenchymal cells for _ organization and _. e.g. dense bodies in smooth muscle and z-disk in skeletal muscle
Class IV- _ (NFL, NFM, NFH) in neurons for _ _. e.g. axon
Class V- _ in nucleus for nuclear _ and _. e.g. nucleus

Back 48

keratins
strength and integrity
desmin, GFAP, vimentin
sarcomere, integrity
neurofilaments
axon organization
lamins
structure and organization

Front 49

All IF proteins have a conserved _ _ and are organized similarly into filaments.
They are _-_ with globular N and C-terminal domains. Monomers form _ _ . Dimers form staggered _-_ _. therefore IFs are _, unlike MFs and MTs fig 18.45

Back 49

conserved core
alpha-helical
parallel dimers
anti-parallel tetramers
symmetric

Front 50

All IF proteins have a conserved core domain and are organized similarly into filaments. Tetramers join end-to-end to form _. Four protofibrils coil around each other to form an _. coiled like a _. Globular N and C domains protrude from IF surface hence the _ _. fig 18.45

Back 50

protofibrils
IF
rope
beaded appearance

Front 51

Intermediate filaments are dynamic polymers in the cell: although IFs are more _ than MFs and MTs, they undergo assembly and dissambly in vivo.
_ subunits slowly undergo exchange
The nuclear _ disassembles during nuclear envelope breakdown during _ and this is regulated by lamina _. fig 18.46

Back 51

stable
Keratin
lamina
mitosis
phosphorylation

Front 52

Defects in lamins and keratins cause many diseases: _ _ occurs when keratin is absent in epidermal cells so they are more susceptible to mechanical damage and the epidermis readily separates from the underlying dermal layer.
The role of keratin is purely _. IFs also anchor cells to the matrix at cell juctions, giving _ _ to epithelial sheets.

Back 52

excessive blistering
structural
mechanical strength

Front 53

Defects in lamins and keratins cause many diseases: lamin assoc diseases: include muscular _ and premature _.

Back 53

dystrophies
aging

Front 54

_ and associated proteins stabilize sarcomeres in skeletal muscle. Structural role is not involved in _ _.

Back 54

desmin
force generation

Front 55

Intermediate Filaments- associated proteins (IFAPs) contribute to _ _.

Back 55

cellular organization