Lecture 14: Cytoskeleton Flashcards

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1
Q

what is the function of the cytoskeleton 3

A

provides structural support
maintains cell shape
enables cellular movement and organisation

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2
Q

what is the cytoskeleton composed of 3

A

3 major types of protein:
actin microfilaments
microtubules
intermediate filaments

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3
Q

what other processes is the cytoskeleton involved in 4

A

cell division
intracellular transport
signal transduction
cell adhesion

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4
Q

describe microtubules 3

A

cylindrical, tube like
diameter of 25nm is biggest component
made of a-tubulin and b-tubulin protein subunits

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5
Q

what does a-tubulin and b-tubulin make together

A

heterodimers

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6
Q

how do these heterodimers work 2

A

assemble head to tail creating protofilaments
13 parallel protofilaments associate laterally to form a microtubule

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7
Q

explain polarity within microtubules 2

A

microtubules exhibit polarity with a “plus” and “minus” end
the plus end is the site of rapid growth, whereas the minus end is more stable

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8
Q

what regulates the rapid assemble and disassemble of microtubules

A

GTP hydrolysis GTP -> GDP + Pi

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9
Q

what is the function of microtubules 3

A

intracellular transport
maintenance of cell shape
formation of the mitotic spindle during cell division

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10
Q

explain the role of microtubules in the formation of the mitotic spindle

A

non-dividing cells = microtubules radiate from microtubule organising center (MTOC) near the nucleus
minus end anchors at MTOC and plus end extends towards end of cell
during mitosis centrosomes duplicate and move to ends of cell with spindle microtubules extending from them
some spindle microtubules attach to kinetochores of xsomes
others interact with microtubules from the opposite centrosome
microtubule dynamics facilitate xsome alignment and segregation = equal distribution of genetic material to daughter cells

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11
Q

what is dynamic instability

A

a process characterised by alternating phases of polymerisation and depolymerisation

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12
Q

what is dynamic instability regulated by in microtubules

A

GTP and GDP bound tubulin at the end of the microtubules
GTP-bound b-tubulin is incorporated into the growing end and the GTP is hyrdolysed into GDP
presence of GTP bound tubulin caps promotes growth

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13
Q

what are intermediate filaments

A

rope like structures
second largest component
diameter of 10nm

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14
Q

what are intermediate filaments composed of 6

A

various proteins divided into 6 classes
type 1 - acidic keratin
type 2- basic keratin
type 3 - vimentin, desmin, glial fibrillary acidic protein
type 4 - neurofilaments
type 5 - nuclear lamins
type 6 - nestin

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15
Q

what does each intermediate filament protein have

A

conserved central a-helical rod domain flanked by non helical head and tail domains

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16
Q

how do intermediate filaments assemble

A

assemble into parallel dimers through coiled-coil interactions between their a helical rod domains
these dimers arrange antiparallel to form staggered tetramers/ protofilaments
8 protofilaments form a cylindrical intermediate filament with non- polar, elongated structure

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17
Q

give 2 distinct differences between intermediate filaments and microtubules and actin filaments

A

do not exhibit polarity
are not directly involved in intracellular transport or motor protein based movements

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18
Q

what is significant about the intermediate filaments

A

their unique structure allows them to withstand significant tensile forces and maintain cell integrity under mechanical stress

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19
Q

what is the function of intermediate filaments 7

A

1 maintain cell shape and integrity by distributing mechanical stress evenly preventing deformation and damage to cellular components
2 cell to cell and cell to extracellular matrix adhesion by linking cytoplasmic structures to cell junctions and focal adhesion
3 nuclear positioning and anchoring, nuclear lamins provide structural support to nucleus and connecting it to cytoskeleton
4 muscle cells desmin connects myofibrils to sarcolemma - maintains structural integrity of muscle fibers & force transmission
5 nerves - neurofilaments - structural & functional properties of neurons. GFAP - glial fibrillary acidic protein for glial cells
6 regulation of cell signalling pathways - interact with signaling molecules and influencing their localisation and activity
7 involved in various cellular processes, including cell migration

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20
Q

describe actin microfilaments

A

thinnest component
diameter of 7nm

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21
Q

what are actin filaments composed of

A

globular actin (G-actin) protein subunits
assemble into helical polymer called filamentous actin (F-actin)

22
Q

how do actin filaments exhibit polarity

A

they have a “barbed” plus end where subunits are added rapidly
“pointed” minus end more stable

23
Q

explain G-actin

A

monomeric form of actin
highly conserved protein
central role in various cellular processes
has ATP/ADP binding sites for interactions

24
Q

explain F-actin

A

linear polymer
formed by head to tail assembly of G actin monomers
flexible and dynamic helical filament
assembly process is ATP-dependent

25
Q

how are actin filaments formed

A

1 nucleation - assembly of g-actin into a stable nucleus- a trimer = this is the rate limiting step nucleus has high energy barrier
2 addition - g actin monomers bound to ATP associate with plus end extending it

26
Q

what is treadmilling in the context of actin filaments

A

the dynamic turnover of actin filaments
addition of g actin monomers at the barbed end is balanced by dissociation of ADP- bound actin subunits from pointed end
maintains constant filament length with directionality

27
Q

what is the formation of filaments regulated by

A

actin binding proteins e.g Arp2/3 complex, tropomyosin

28
Q

explain the function of actin binding protein

A

organisation, dynamics and function of actin filaments
capping proteins regulate addition or loss of actin subunits ensuring stability
cross link proteins organising them
motor proteins interact with actin filaments to generate force

29
Q

what are motor proteins

A

specialised proteins that convert chemical energy-> mechanical

30
Q

what are the major motor proteins

A

myosins
kinesins
dyneins

31
Q

what is the conserved motor domain for in myosins

A

for actin binding and ATP hydrolysis with a variable tail domain that binds to cellular cargoes to move

32
Q

what forms the sarcomere

A

myosin class 2 assemble into bipolar thick filaments which interact with actin

33
Q

what do myosin 1 and myosin 5 do

A

vesicle transport
cell migration
cytokinesis

34
Q

what is myosin function regulated by

A

phosphorylation
calcium binding
interactions with other proteins such as tropomyosin and troponin

35
Q

what are the kinesins characterised by

A

conserved motor domain with a microtubule binding site and ATP binding site which is responsible for the driving movement along microtubules

36
Q

what does it mean that kinesins are plus end directed motors

A

they move towards the plus end of microtubules

37
Q

what causes the walking motion with kinesins

A

two motor domains alternate between microtubule bound and unbound states while hydrolysing ATP

38
Q

what are kinesins also involved in

A

mitosis - formation and positioning of the mitotic spindle
xsome alignment
segregation os ister chromatids to daughter cells
transport of organelles, vesicles

39
Q

what are dyneins

A

move laong microtubules and convert chemical energy from ATP to mechanical work for cellular transport and mitosis

40
Q

are dyneins plus or minus end directed motors

A

minus end directed motors

41
Q

what are dyneins classified into

A

2 major groups:
cytoplasmic dyneins
axonemal

42
Q

what are cytoplasmic dyneins involved in

A

intracellular transport and mitosis

43
Q

what are axonemal dyneins involved in

A

the beating of cilia and flagella (kinky hehhe)

44
Q

what does it mean that dyneins are processive motors

A

they take multiple steps along microtubules without dissociating allowing them to cover long distances

45
Q

why is dynein mediated transport important

A

essential for proper positioning and function of organelles like golgi apparatus, endosomes, lysosomes and vesicles

46
Q

what are focal adhesions

A

specialised multi-protein complexes that connect actin cytoskeleton to extracellular matrix
faciliate cell adhesion
migration
mechanosensing

47
Q

what are integrins

A

transmembrane receptors that play important part in focal adhesions by binding ECM proteins to the actin cytoskeleton

48
Q

what is the function of focal adhesions

A

important for mechanotransduction- the process by which cells sense and respond to mechanical forces
they convert mechanical stimuli into biochemical signals that affect cellular processes such as gene xpression migration and differentiation

49
Q

what are cytoskeletal components regulated by

A

signaling pathways

50
Q

what does the Rho signalling pathway do

A

control actin polymerisation
stress fiber formation
cell migration

51
Q

what does the cytoskeleton do in cell division 4

A

organises mitotic spindle
formation and constriction of cleavage furrow during cytokinesis
ensures proper spindle assembly and xsome segregation
movement of xsomes along microtubules

52
Q

what is the role of cytoskeleton in wound healing

A

drives cell migration and shape changes necessary for cells to migrate into wounded area
actin polymerisation generate lamellipodia and filopodia which enable cells to move towards the wound
formation and turnover of focal adhesions provide traction for cell migration
cytoskeletal remodeling modulate cell migration and wound healing processes
activate signalling pathways that regulate cell proliferation, migration and differentiation