cell cytoskeleton and cell adhesion Flashcards

1
Q

describe resistance to stress - epithelial cells

A

in epithelia tissues cell cytoskeletons are linked by cell-cell + cell-matrix junctions are the stress bearing components

mechanical stress transmitted from cell-cell by cytoskeletal filaments anchored to cell-matrix + cell-cell adhesion sites

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2
Q

describe resistance to stress in connective tissues

A

in connective tissue the extracellular matrix = main stress bearing component
extracellular matrix directly bears mechanical stresses of tension + compression

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3
Q

describe cell adhesion to ECM etc

A

cell adheres to a soft surface (ECM, basal membrane etc) through adhesion domains
cell cytoskeleton connects to these adhesion domains

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4
Q

what are the cytoskeleton functions

A

bones + muscles of the cell
provides structural framework for the cell + organise interior
facilitates intracellular transport
supports cell junctions + cell adhesions
transmit signals
permits cell mobility + division

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5
Q

what is the cytoskeleton important for

A

cell movement + contractility
cell division + intracellular movement
maintaining tissue intergrity

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6
Q

describe dentinogenesis imperfecta type I

A

occurs in 50% of pts with osteogenesis imperfecta
oral manifestation of deficient collagen I production -> abnormal dentine
teeth = discoloured
- blue-grey / yellow-brown
-translucent
-weaker than normal -> prone to breakage + loss

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7
Q

what is the length of microfilaments

A

8nm

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8
Q

what is the length of microtubules

A

25nm

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9
Q

what is the length of intermediate filaments

A

10nm

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10
Q

what is the filament for cell movement and contractility

A

microfilaments

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11
Q

what is the filament for cell division and intracellular movement

A

microtubules

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12
Q

what is the filament for maintaining tissue integrity

A

intermediate filaments

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13
Q

microtubules size

A

25nm
tubulin

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14
Q

microfilaments size

A

8nm
actin

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15
Q

intermediate filaments size

A

10nm
keratin
vimentin
desmin

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16
Q

what are microfilaments made of

A

actin

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17
Q

what are microtubules made from

A

tubulin

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18
Q

what are intermediate filaments made from

A

keratin
vimentin
desmin

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19
Q

describe microfilaments

A

thinnest of cytoskeletal elements - 8nm diameter
6 actin genes in humans - 4 encoding muscle + 2 cytoskeletal actins
actin = all eukaryotic cells
in epithelial cell sheets - at the periphery (actin cortex) + interact with adhesion junctions + focal adhesions

F ACTIN
- formed = polymerisation of actin subunits - G actin
2 intertwined strands of actin = assemble into bundles- 2D+3D networks = with other proteins
rapidly assemble + disassemble
flexible
important for cell migration

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20
Q

what are FAs

A

focal adhesions

21
Q

what are AJs

A

adhesion junctions

22
Q

what happens during cell migration - microfilaments

A

new actin microfilaments form - leading edge of cell
= lamellipodium
incorporated into DAs - anchor L to underlying substratum (matrix proteins) by integrins

23
Q

what is the edge of the cell called

A

lamellipodium

24
Q

describe protrusion

A

actin polymerisation at the leading edge pushes out a lamellipodium

25
Q

describe attachment

A

new FAs formed at leading edge
incorporate actin filaments
attach lamellipodium to substratum
creates tension at front of cell

26
Q

describe detachment

A

contraction of actin cortex creates tension
relieved when FAs at the back of the cell are degraded
back of cell moves forward

27
Q

what are the steps involved in moving the cell forward step-wise

A

protrusion
attachment
detachment

28
Q

describe microtubules

A

thickest
25nm - diameter
subunits = α-tubulin/β-tubulin heterodimer
multiple α and β tubulin genes in humans
tubulin = all eukaryotic cells
important in cell division , movement of organelles, vesicles in cell
hollow cylinders, long, straight
rapidly assemble/disassemble
formed by polymerisation of α-tubulin/β-tubulin heterodimers
typically microtubules grow out of centrosome + towards periphery - MICROTUBULE POLARITY - creating transport tracks

29
Q

how are microtubules formed

A

are formed by polymerisation of α-tubulin/β-tubulin heterodimers

30
Q

what is the shape of microtubules

A

hollow cylinders
long
straight

31
Q

what are microtubules important for

A

cell division
movement of organelles
vesicles within a cell

32
Q

how to microtubules typically grow

A

out of centrosome
towards periphery - MICROTUBULE POLARITY
creating a system of transport tracks

33
Q

describe intermediate filaments

A

thicker than microfilaments, thinner than microtubules
10nm = diameter
made from 3 proteins depending on cell type:
- keratins, desmin, vimetin
multiple keratin genes in types
in epithelia cell sheets IFs interact with desmosomes + hemidesmosomes
gives cells mechanical strength + mainly tensile

34
Q

what are the 3 types of proteins intermediate filaments are made from

A

keratin
desmin
vimetin

35
Q

what cells do keratins make up

A

epithelia

36
Q

what cells do desmins make up

A

desmin

37
Q

what cells do vimetin make up

A

mesenchymal cells

38
Q

intermediate filaments - keratins

A

rope like fibres
coiled-coil heterodimer - type I + 11 keratin
type I + II keratin chains orientated in parallel + intertwined a coiled coil rod
dimers = antiparallel staggered manner + packaged together in helical array = form rope-like filament
strong
mutations in cytokeratins = interfere with formation of keratin filaments
-> eptihelia = highly vulnerable to mechanical injury
-> EB simplex

39
Q

what is EB

A

epidermolysis bullosa

40
Q

describe basal lamina + hemidesmosomes

A

thin, tough mat of specialised extracellular matrix
underlines all epithelial cell sheets
synthesised primarily by epithelial cells
dynamic sieve to control molecular passage
complex structure of 2 layers - lamina lucida + lamina densa
major components - laminin + collagen IV

41
Q

describe type IV collagen

A
  • forms flexible sheet
  • with chicken-wire configuration
  • in lamina densa & binds laminin
  • connects to anchoring fibres
  • adhesive glycoprotein laminin - in lamina lucida- binds epithelial cells - fixing them to collagen sheet
  • laminin - thought to be primary organiser of basal lamina with cell + collagen binding domains
42
Q

describe desmosomes

A
  • mediate cell-cell adhesion and anchor keratin intermediate filaments to membrane
  • circular/oval areas of adjacent cell membranes, adhering by attachment plaques
    • consisting of desmoplakin, plakophilin and plakgoglobin
  • link intermediate filaments to cadherins
    • class of adhesive proteins
    • penetrate membrane + enter the intracellular region of the demosome
  • desmosomal cadherins
    • desmocollins - DSC
43
Q

what is blistering disease

A
  • disruption of desmosome-IF or hemidesmosome-IF interactions can result in:
    • loss of cell-cell adhesions (pemphigus)
    • loss of cell matrix adhesion - pemphigoid epidermolysis bullosa
44
Q

describe pemphigus vulgaris

A
  • autoimmune blistering disease of skin and oral mucosa
    • caused by defective cell-cell adhesion
    • desmosomes affected
  • pathogenic autoantibodies → DSG3 - blistering occurs in the lower epidermis
  • type usually begins with blisters in the mouth + then on skin/ genital mucous membranes
  • blisters typically painful but don’t itch
  • often spotted first by dentist
  • epidermis severely compromised so prognosis is poor
  • almost always fatal if untreated due to fluid loss + infection
45
Q

what does pemphigus vulgaris usually begin with

A

blisters in the mouth
then on skin/genital mucous membranes

46
Q

what is pemphigus vulgaris caused by

A

defective cell-cell adhesion
desmosomes affected

47
Q

what is mucsois membranes pemphigoid

A
  • auto-antibodies attack hemidesmosomes or basal lamina molecules
    • eg. BP230, BP180
  • loose basal lamina - epithelial adhesion
  • sub-epithelial blisters - mucosa involved -mostly oral, also eyes
  • red or ulcerated patches on inner cheeks, gums, hard palate
  • red, shiny, ulcerated gums
48
Q

what does mucsois membranes pemphigoid do to the body

A

auto-antibodies attack hemidesmosomes or basal lamina molecules

49
Q

describe the ECM

A
  • cells can bind to each other directly or via extracellular matrix which they secrete around them
  • in connective tissue ECM is abundant + caries the mechanical load
    • secreted by fibroblasts
  • composed of ground substance + fibres
  • fibres consist of collagen + elastin
  • responsible for mechanical strength
  • ground substance is clear viscous substance composed of highly hydrophillic proteoglycans that trap water + form hydrophylic gels
    • provides resistance to compression
  • glycoproteins - eg. fibronectin - bridge between matrix (collagen) and cells
  • growth factor, cytokines + inflammatory mediators