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Flashcards in Exam Deck (111):
1

ARP 2/3 complex

actin- nucleates assembly to form a web and remains associated with the minus end.

2

profilin

actin- binds substrate, speeds elongation

3

tropomyosin

actin- stabilizes filaments

4

capping protein

actin- prevents assembly and disassembly at plus end

5

gelsolin

actin- severs filaments in the middle and binds to plus end
binds along side actin activated by high [Ca]

6

cofilin

actin- binds ADP actin filaments, accelerates disassembly more at the - end
binds along side
important for directed growth of development

7

tropomodulin

actin- prevents assembly and disassembly at minus end

8

thymosin

actin- binds subunits, prevents assembly

9

formin

actin- nucleates by capturing 2 monomers and remains associated with the plus end
actin is bundled in straight unbranched
strongly enhanced when bound to G-actin-profalin

10

fimbrin

actin- non- contractile. actin cross linking protein that creates tightly packed bundles and excludes myosin - structural stability

11

alpha - actinin

actin- bundles actin filaments more loosely and allows myosin entry. myosin 2 is a motor protein that interacts with actin to create contractile filaments

12

filamin

actin- forms a loose and highly viscous actin gel, clamps actin filaments at right angles
used to make lamellipodia

13

spectrin

2 actin filament binding sites, form regular array on inner surface of PM, creates web of actin
attached to peripheral membrane protein that in turn attach to integral membrane proteins - results in a strong yet flexible cortex

14

ERM family

actin - involved in maintenance of cell polarity, exocytosis, endocytosis; c termini binds to sides of actin filaments, N- termini binds to cytoplasmic face of transmembrane GP

15

actin structure

globular monomer, binds to ATP, highly conserved in eukaryotes
two parallel proteofilaments wrap around each other in an alpha helix

16

critical concentration

concentration at which monomeric subunits are in equilibrium with each other
rate of addition = rate of loss

17

microtubule (MT) structure

hollow, 13 protofilaments each composed of alternating alpha (+end) and beta (-end) subunits. both have GTP binding sites but it is only hydrolyzed in beta
b/c of multiple contact points the addition and loss of subunits are at the ends of filaments

18

treadmiling

at specific intermediate [subunit] the length of the filament doesnt change, the rate of loss at one end matches the rate of addition at the other

19

dynamic instability

a single end can suddenly change to D form, then begin to shrink even though [monomer] stays constant. if subunit addition suddenly replaces a GTP bound subunit on the shrinking end, will convert back into a growing MT
rapid conversion b/w growing and shrinkage at the same [subunit]

20

taxol

stabilizes MT by binding along filaments

21

nocodazole

depolymerizes MT by binding tubule subunits

22

colchicin

depolymerizes MT by caping filament ends

23

latrunculin

depolymerizes actin by binding to actin subunits

24

cytochalasin B

caps actin filaments plus end

25

phalloidin

stabilizes actin by binding along filaments

26

Gamma-tubulin

nucleates MT growth, part of MTOC
gamma-TuRC: gamma-tubulin + 2 other proteins form a ring thought to act as template

27

+ TIP

MT: specifically bind to plus end and disassociate when shrink.
remain associated with growing plus ends and can link them to other structures such as membranes

28

XMAP215

MT: stabilizes plus ends and accelerates assembly binds free tubulin subunits, delivers to plus end, promotes polymerization

29

MAPS

MT: stabilizes by binding along sides, regulates stability and dynamics, mediate MT interactions, can regulate how tightly MT are bundled

30

katanin

MT: dimer, small subunit hydrolyzes ATP and preforms severing
large subunit directs to centrosome
releases MT from MTOC

31

kinesin 13

MT: induces catastrophe and promotes disassembly

32

stathmin

MT: bind 2 tubulin heterodimers, prevents their addition onto ends of MT, decreases [] when activated increases shrinkage
inhibited by phosphorlytion

33

gamma -TuRC

MT: nucleates assembly and remains associated with the minus end, also caps the the minus end

34

kinesin

superfamily of motor proteins, dimeric, ATP hydrolysis to drive movement. anterograde transport move in plus direction

35

dyneins

specific to minus end
cytoplasmic dyneins: homodimer, transport of mRNA and organelles as well as intraflangellar transport
axonemal (ciliary) dyneins: come as monomer, heterodimers, or heterotrimers. involved in beating of cilia and flanella
retrograde transport moving towards minus end

36

axoneme

9 doublets of MT (one partial one complete) around pair of single MT = 9+2 arrangement

37

ciliary dynein

forms bridges b/w neighbouring doublet. when activated dynein moves towards the minus end causing the MT to slide past one another, but b//w te MT are crossed-linked siding does not happen and the force generated creates a bend

38

basal bodies

firmly roots cilia and flangella at cell surface
have nine triplets of MT

39

intermediate filaments (IF)

only in some metazoans
predominant in cells subject to mechanical stress, related to nuclear lamins much more divers than actin and tubulin
creates rope like structures

40

how are IF bundled

all IF have a conserved alpha helical domain that forms extended coiled-coil b/w two monomers
pair of parallel dimers associate into anti-parallel staggered tetramers, no nucleotide binding, no polarity, difficult to break can be stretched to 3X original strength

41

keratins

heterodimeric filament subunit = one acidic and one basic/neutral, cross-linked networks with S-S bonds that survive death, impart mechanical strength to epithelial cells anchoring to cell-cell junctions , can give clues to the origin of tumours

42

nerurofilaments (NF)

found in high [] along axons, heteropolymers, level of NF expression determines axon diameter

43

plakins

cross-link with other cytoskeletal components, bundles IF also links them to actin and MT, attaches IF to adhesive structures at PM
mutations lead to disorders that combine epudermolysis bullosa, muscular dystrophy, and neurodegenration

44

SUN-KASH bridges

SUN-KASH protein complexes connect the interior of nucleus with actin and MT
proteins on the inner NM interact with nuclear lamina, chromosomes
proteins on outer NM interact directly with actin and indirectly with MT
mutations underlie progeruas

45

septin

STP binding proteins, assemble into nonpolar filaments, form rings and cages
acts as a scaffold to compartmentalize membranes, act in cell division, migration, vesicle trafficking
assembles at base of primary cilia

46

how does a cell crawl?

protrusion - actin-rich structures are pushed out from the front of the cell
attachment - actin cytoskeleton attaches to the substratum across the PM
traction - the bulk of the cytoplasm is drawn forward

47

protrusion

filopodium - long, thin, 1D, bundled actin,growth cone of neuron
lamellipodium - wide, 2D sheet, cross-linked mesh of actin, epithelial cells and fibroblasts
invadopodia (podosomes) - larger, 3D blob, important for cells crossing the tissue barrier
all are filled with filamentous actin

48

maintaining unidirecional movement

filament nucleation at leading edge - new growth pushes PM forward
depolymerization occurs at sites behind the leading edge
cofilin binds preferentially and cooperatively to D actin newly formed filaments more likely to be in T form and resistant to cofilin delayed ATP hydrolysis basis for unidirectional movement

49

bringing up the lagging edge

focal adhesions, involve intergrins, link migrating cell to extracellular matrix/substratum
sarcomere-like contractions of myosin pull actin filaments into new orientation - if engaged, integrins respond and cell body moves forward

50

regulation of actin cytoskeleton rearrangement

requires some form of cell polarization - a signal is required to initiate movement, establish a front and back
surface receptors function to elicit actin rearrangements all work via rho family

51

RHO proteins

molecular switches, small monomeric GTPases, active in GTP bound state, members of RAS super family.
CDC42 - > filopodia
RAC -> lamellipodia
RHO -> stress fibers and focal contacts

52

apoptosis role in tissue homeostasis

cell division and cell death must be balanced .all cells are poised to commit suicide. PCD genetically determined
most but not all PCD occurs by apoptosis
increases cell proliferation or decreases cell death favours cancer

53

morphology of apoptotic cells

cells shrink and condenses, cytoskeleton collapses, nuclear envelop disassembles, cell surface "blebs", cell breaks up into membrane enclosed pieces

54

dealing with dead cells

recognized by phagocytic cells (macrophage) but sometimes neighbouring cells can engulf the apoptotic cell
recognized based on a specific single - phosphatidylserine is exposed to outer membrane leaflet
when cells die via apoptosis and are cleared by immune cells there is no inflammatory response

55

why bother with PCD

essential role in development and quality control
on gong role in homeostasis

56

what are CAPases

cysteine aspartate proteases - have a cys in their active site and cleave after tetrapeptide asp
most not all CAPases mediate PCD some mediate inflammatory and immune response

57

the extrinsic activation pathway of apoptosis

fas ligand on surface of cytotoxic lymphocyte binds to fas death receptor on target cell > this triggers death-inducing signalling complex (disc) to form in the cytoplasm of target cell > activation of capases 8
cells are able to block this

58

generating apoptosome

cytC binds to APAF-1 which undergoes a conformational change and oligomerizes into the apoptosome > recruitment of capases 9 . activated executioner capase

59

BCL 2 family

apoptotic effectors, BCL 2 gene is activated by chromosomal translocations in non-hodgkin lymphomas and solid tumors - gene is associated with blocking PCD (anti-apoptotic)
family members regulate intrinsic pathway by controlling release of cyto c and other IMS proteins

60

BAX and BAK

promote apoptosis
stimuli activates BAX/BAK > aggregate to form oligomers in OMM > induce cyt c
at least one is needed

61

Bcl 2 and Bcl -XL

anti- apoptotic
The antiapoptotic Bcl2 family proteins inhibit apoptosis mainly by binding to and inhibiting pro-apoptotic Bcl2 family protein
prevent inappropriate [ca] release
blc 2 binds bax though BH3 domain and prevents oligomerization preventing mitochondrial permeation
the more bcl 2 on the OMM the more bax is needed for PCD

62

inhibition of apoptosis

1) increased production of anti-apoptotic blc 2
2) inactivation of pro-apoptotic BH 3 -only protein
3) inactivation of anti-IAP

63

desomosome

nonclassical cadherin attached to IF for cell-cell adhesion
important in vertebrates not in invertebrates, plentiful in high stress tissue

64

adherens juction

classical adherins attached to actin filaments

65

actin - linked

cell-matrix junction linked to integrins by actin

66

hemidesmosomes

integrins attached to IF forming cell-matrix junction

67

tissue segregation

cells tend to sort themselves out according to the type of cadherins and amount of cadherin expressed. cells with higher levels will adhere more strongly and end up internally

68

twist

negitivly regulates e-cadherin. tuning on twist results in promotes epithelial-mesenchymal transition. blocking twist stops cancer cells from spreading by forcing them back to epithelial

69

how are cadherins linked to cytoskeleton

intracellular domain of cadherins are indirectly linked to cytoskeleton by catenin
p120 and beta catenin into actin in adherence junctions
gamma catenin (plackoglobin) IF in desmosomes

70

assembly of adherens junction

membrane protrusions intimate cell-cell contact > actin and cadherin recruitment expands junctions > actin remodeling and muscle myosin recruitment expands adherens junction

71

zonula adherens

junctions are organized as a continuous adhesion belt tethered to bundles of contractile actin, forms trancellular network , entire sheet of cell act as a co-ordinated unit

72

role of tight/occluding junctions

environment on apical side is different from basel
prevent molecules from leaking back into the original space after being transported across the epithelia and prevent basel and apical membrane proteins from diffusing

73

forming the tight junction

claudins - form sealing strands
occludins - not essential for structural or assembly but limit permeability
tricellulin - also required to prevent leakage

74

gap junctions

plasmodesmata in plants
bridges gaps b/w adjacent cells to create a direct channel and a physical connection , small molecules can move freely
cells are metabolically and electrically connected

75

composition of gap junctions

connexinns (predominate in vertebrates), innexins (invertebrates) un related in sequence but similar in shape six connexins for a hemichannel = connexon
when connexons in PM of 2 cells are in contact they align to form a continuous channel

76

extra cellular matrix

tissues are made of cells + macromolecules
produced by cells locally
provides physical strength

77

Glycoaminoglycans (GAG)

unbranched polysaccharides composed of repeating disaccharides
first sugar is GlcNAc or GalNAc usually sulfated
second is usually uronic acid
highly negatively charged - very hydrophilic

78

GAGs are characterized in to 4 groups

hyaluronan
chondroitin sulfate
heparan sulfate
keratin sulfate

79

how do gags contribute to matrix characteristics

huge volume relative to mass form hydrated gels at low []
attracts a cloud of cations esp Na+ that are osmotically active - large amounts of water can be sucked into the matrix
turgor - allows our bodies to resist pressure

80

hyaluronan function

simplest of GAGs, no sulfation,identical disaccharide, synthesis in in PM, no protein core
compression resistance, space filler in embryogenesis, forces change in shape and structure, high amounts is wound healing

81

how are GAGs linked to the core proteins

except for hyaluroan
core protein of proteoglycan starts in ER polysaccarides assemble in golgi, linkage tetrasaccharide is attached to ser side chain (o-linked)

82

glycoproteins (GP) va proteoglycans (PG)

PG - at least one of the sugars must be GAG up to 95% carbs by weight, long unbranched chain
PG - 1-60 %

83

collagen

fiberous protein, major component of skin and bones, long stiff triple helix, pro stabilizes helix gly packing of 3 helices

84

type 1 collagen

most common, skin and bones fibrillar (fibril-forming), long rope like structure with few interruptions, formed into fibrils after secretion

85

type 9 and 17 collagen

fibril-associated collagens decorate surface of collogen fibrils link fibrils to each other and to other ECM components

86

type 4 collagen

network forming, major component of basal lamina

87

type 7

forms dimers, assemble into anchoring fibrils, hellp attach BL to CT

88

collagen fibril assembly

1. synthesis of pro-alpha-chain
2. hydroxylation of selected pro and lys
3. glycoslation of selected hydrolys
4. self assembly of 3 pro-alpha-chains
5. procollagen triple helix formation
6. secretion
7. cleavage of pro peptides
8. self assembly into fibril
9. aggregation of collagen fibrils to form a collagen fiber

89

how does collagen resit tensile forces

various diameters, organized in different patterns - resistance in multiple directions
cells can regulate disposition of collage molecules after secretion by guiding fibril formation in close association with PM

90

fibril-associated collagen

mediate interaction of collagen fibrils with each other and other matrix macromolecules to determine organization
types 9 and 17: tipple helix interrupted by 1 or 2 short non-helical domains, increases flexibility
do not aggregate to for fibrils rather bind periodically to surface of fibrils formed by collagen
type 9 binds type 2 collagen in cartilage, cornea
type 17 binds to type 1 in tendons

91

how are collagen fibrils organized

mechanical interactions affects CT architecture
fibroblasts in culture mix with meshwork of collagen fibrils forming a gel, tug and draw in collagen shrinking the gel
cluster of fibroblasts surround selves with capsule of densely packaged collagen fibres around circumference

92

elastic fibres

resilience to recoil after transient stretch; interwoven with collagen to limit extent of stretch preventing tearing
main component: elastin, highly hydrophobic

93

tropoelastin

a precursor, secreted into ECS and assembled into fibres close to PM with hight degree of cross-linking

94

what allows elastin to stretch

composed of 2 short segments that alternate along peptide chain: hydrophobic segments responsible for elastic properties, ala and lys rich alpha helix form cross-links b/w adjacent molecules

95

other components of elastic fibres

core covered by sheath of microfibrils - appear before elastin, may form the scaffolding for elastin . may be present in absence of elastin (holds eye lens in place)

96

microfibril composition

several different GP one of which is fibrilllin - binds to elastin, essential for integrity of elastic fibrils

97

fibronectin fibrils

soluble (circulating in blood) or insoluble (ECM)
only assembles in vivo on curface of cells with appropriate fibronectin binding proteins (inegrins) - provides linkage from out fibronectin to inner actin cytoskeleton - linkage transmits tension

98

function of BL

structural and filtering, develops cell polarity, organized proteins in adjacent PM, affects cell survival, proliferations, and differentiation, acts as a high way for migrating cells
keeps epidermal cells attached to CT

99

forming BL

synthesized from components contributed by both epithelial cells and cells of the underlying CT

100

BL composition

varies with cell type.
contains GP - laminin, type 4 collagen and nidogen and the PG perlecan
other molecules frequently in the meshwork are collagen 17 and fibronectin
primary organizer is laminin - first to appear in development

101

laminin 1

classical laminin. large flexable teterotrimer with chains head by S-S bonds
self-associates in vitro into a network, binds to other components of bl to form an organized sheet

102

BL tensile strength

assembly into 2D sheet
multiple binding domains for 3 other type 4 collagen, nidogen and prelacan serve as linkers to connect laminin and collagen networks
laminin first join together while bound to cell surface receptors

103

BL diverse functions

molecular filter - prevents macromolecules passage from blood to urine
barrier to movement of cells - beneath epithelium, prevents fibroblasts from contacting epithelium but allows lymphocytes and neural processes
tissue regeneration after injury - lamina survived provides a scaffold along which regenerating cells can migrate

104

how id the bl degraded

continuous turnovers in ECM
enables cell division while embedded in matrix, enables travel through matrix required for cells escaping for normal growth and WBC infiltration
degraded by extracellular proteases that act close to cells that produce them
matrix metalloproteinases - ca and zn dependent
serine protease - highly reactive ser at active site
only secreted in responds to a signal together they can degrade collagen, laminin, fibronectin

105

integrin structure

anchor a cell to ECM; transmit signal from outside to inside and vice versa
alpha and beta units have short c-terminal intracellular domains - interacting with other anchoring proteins and actin cytoskeleton

106

integrins in hemidesmosomes

extra cellular portion of dimer binds to specific AA sequence in ECM molecules or on neighbouring cells
can binds to actin through talin or more likly bind to keratin and anchor proteins plectin and dystonin

107

switching b/w intragrin conformations

in order to rapidly change adhesive properties
integrins can undergo conformational changes to active or inactive forms - activated by inside -out activation or outside-in
structural changes at one end is coupled to the other - extension in extracellular domains and separation in intracellular domain

108

what is inside out activation

triggered by intracellular regulatory molecules (PIP) that activate talin so it binds to beta chain strongly
PIP is produced in response from an outside signal

109

how do intragrins affect cellular adhesion

intrigrins differ from typical cell surface receptors b/c they bind ligand with low affinity and are present at higher []

110

anchorage dependance

many cells will not grow/proliferate unless attached to ECM, some require ECM for survival - ensures survival and proliferation is only in appropriate situations, mutations in this may lead to cancer
cells forced to spread over a large area by multiple adhesions at separated csites grow better

111

focal adhesion kinase (fak)

multiple signalling paths involving integrin.
FAK recruited by intracellular anchor proteins such as talin