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cell cytoskeleton and cell adhesion Flashcards

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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

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A

focal adhesions

21
Q

what are AJs

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A

adhesion junctions

22
Q

what happens during cell migration - microfilaments

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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

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A

lamellipodium

24
Q

describe protrusion

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A

actin polymerisation at the leading edge pushes out a lamellipodium

25
describe attachment
new FAs formed at leading edge incorporate actin filaments attach lamellipodium to substratum creates tension at front of cell
26
describe detachment
contraction of actin cortex creates tension relieved when FAs at the back of the cell are degraded back of cell moves forward
27
what are the steps involved in moving the cell forward step-wise
protrusion attachment detachment
28
describe microtubules
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
how are microtubules formed
are formed by polymerisation of α-tubulin/β-tubulin heterodimers
30
what is the shape of microtubules
hollow cylinders long straight
31
what are microtubules important for
cell division movement of organelles vesicles within a cell
32
how to microtubules typically grow
out of centrosome towards periphery - MICROTUBULE POLARITY creating a system of transport tracks
33
describe intermediate filaments
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
what are the 3 types of proteins intermediate filaments are made from
keratin desmin vimetin
35
what cells do keratins make up
epithelia
36
what cells do desmins make up
desmin
37
what cells do vimetin make up
mesenchymal cells
38
intermediate filaments - keratins
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
what is EB
epidermolysis bullosa
40
describe basal lamina + hemidesmosomes
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
describe type IV collagen
- 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
describe desmosomes
- 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
what is blistering disease
- 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
describe pemphigus vulgaris
- 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
what does pemphigus vulgaris usually begin with
blisters in the mouth then on skin/genital mucous membranes
46
what is pemphigus vulgaris caused by
defective cell-cell adhesion desmosomes affected
47
what is mucsois membranes pemphigoid
- 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
what does mucsois membranes pemphigoid do to the body
auto-antibodies attack hemidesmosomes or basal lamina molecules
49
describe the ECM
- 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

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