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BMS 242 - Advanced Cell and Molecular > Cell adhesion, migration and motility > Flashcards

Cell adhesion, migration and motility Flashcards

1
Q

What does failure of cells to migrate cause?

A

Cell, tissue and organism dysfunction and death

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2
Q

What are the roles of adhesion in development?

A

1) Sperm to oocyte - to transfer paternal DNA
2) Cells begin to express E-cadheirn (adhesion molecules) –> compaction
3) Differences in adhesion cause cells to divide into 2 groups: Inner cell mass (give rise to embyro) and trophoblast (extra-embryonic)
4) Cell implantation into the cellular wall

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3
Q

What is adhesion needed in neural tissue?

A
  • Loss of adhesion from the dorsal nerual tube to form neural crest cells
  • Neural crest cells migrate, so must slightly adhere to substrate (but not too much)
  • Neural crest cels aggregate once finished migrating - changing adhesion properties again
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4
Q

What did studies on sponges by Wilson show?

A
  • When the cells are deaggregated, they are still able to reaggregate and reorganise into separate tissues based upon their adhesion
  • See regionalisation of tissues
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5
Q

What are L cells?

A

Cells that do not aggregate (don’t express cadherins)

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6
Q

What can L cells be used for?

How?

A

To study cadherins:

  • Transfect L cells with transgenes that express different cadherins and monitor their behaviour
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7
Q

How cant the L cells organise when transfected with cadherins?

A

Into different groups with the properties of:

1) Different cadherins
2) Different levels of the cadherin

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8
Q

How do cadherins interact?

A

Bind homophillically to the same cadherin with the extracellular N terminus

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9
Q

Where does Ca2+ bind to cadherins and what does this cause?

A

Binds at the hinge region to stabilise the cadherin and allow it to interact (cant interact when no Ca2+ is bound - floppy)

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10
Q

How can cells modulate levels of interaction and adhesion? (2 ways)

A

1) By the type of cadherin they express

2) By the levels of Ca2+ released into the extracellular environment

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11
Q

How are cadherins organised in the cell?

A

In arrays:

  • In the same cell, interact with partners to form lines
  • On neighbouring cells - they are arranged perpendicular
  • Highly organised: can be adherent on one side of the cell but not the other
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12
Q

What are the 2 types of cadherins?

A

1) Classical

2) Non-classical

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13
Q

How many different types of cadherins are there in vertebrates?

A

Over 100

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14
Q

Where are classical cadherins expressed?

A

In adherens junctions (holds cells together)

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15
Q

What is the structure of classical cadheirns?

A
  • Single pass transmembrane domain
  • Repeated domains
  • Extracellular hinges
  • N terminus extracellular
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16
Q

What are examples of classical cadherins?

A

1) E-cadherin (epithelial)

2) N-cadherin (neural)

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17
Q

What is the first cadherin to be expressed in the embryo?

What is this cadherin important for?

A

E-cadherin

Also important for multicellular function

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18
Q

Where is N-cadherin expressed?

A

In the neural tube and other tissues

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19
Q

What are non-classical cadherins used for?

A

Specialised for unique functions

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20
Q

How are non-classical cadherins different to classical cadherins?

A
  • Contain many different domains that mediate other protein-protein interactions
  • Can have many transmembrane domains
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21
Q

How are non-classical cadherins similar to classical cadherins?

A

Still have homology in their domains

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22
Q

What is an important types of non-classical cadherin and where is it present?

A

Protocadherins in the nervous system

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23
Q

What is the structure of protocadherins?

A

Has many different isoforms which have occurred through alternative splicing of a single gene

24
Q

What 2 things are protocadherins involved with?

A

1) Specifying synapses in the brain - confer complex connectivity
2) Involved in self-avoidance behaviour

25
Q

Why is the expression of cadherins complex?

A
  • Can have strict boundaries
  • Can have graded expression
  • Can have overlapping expression of cadherins
26
Q

What are catenins and where do they bind?

What are their functions?

A

INTRACELLULAR proteins

Bind to the intracellular portion of cadherins to link them to actin in the cytoskeleton

27
Q

What are the 2 roles of catenins?

A

1) Structural role - when bound to cadherin and actin

2) Signalling role

28
Q

How do catenins have a signalling role?

A

When bound to cadherin, beta catenin can control the proliferation of the cell through c-myc

29
Q

How are junctions stabillised when cadherin interacts with the neighbouring cell?

A
  • Interaction forms tension on the cadherin
  • This stretched out the alpha catenin from a folded state to an unfolded state (physical confirmational change of catenin)
  • This confirmational change reveals a binding site for vinculin
  • Vinculin binds to alpha catenin and to other actin filaments to reinforce, stabilise and strenghten the junction (cross-linking)
  • Once stabilised, this interaction can give rise to an entire change within the cell (myosin is attached to actin)
30
Q

What does Rho do when activated?

A

Leads to strong actin filaments forming

31
Q

What activates Rho?

A

Beta-catenin mediated junction formation

32
Q

What happens to actin in a relaxed state?

A

Disorganised threads of actin

33
Q

What does constitutively active Rho lead to?

A

Stress fibre formation

34
Q

Describe the cadherins in the early embryo

A

1) E-cadherin expressed in the very early embryo
- In the epithelium

2) Newly formed mesoderm lose E-cadherin expression
- Able to dissociate and move inside the embryo

3) Neural tube upregulates N-cadherin to replace the E-cadherin
- Allows the neural tube to form

35
Q

Why is E-cadherin expressed in the very early embryo?

A

To pull cells together in the compacting stage

36
Q

What cadherin does the roof plate and floor plate express?

A

Cadherin 6B

37
Q

What cadherin do the neural crest cells express?

A

Cadherin 7

38
Q

Where are selectins expressed?

A

On the cell surface

39
Q

How many transmembrane domains do selectins have?

A

1

40
Q

What do selectins depend upon?

A

Ca2+

41
Q

What do selectins bind?

A

Carbohydrates on neighbouring cells that are expressed specifically on certain cells

42
Q

What are the roles of selectins?

A

In the immune system and neutrophil trapping

43
Q

What is the structure of P-selectin?

A
  • Repeated sequences with different domains at the top

- Intracellular domain linked to actin through anchor proteins

44
Q

What are the domains at the top of P-selectin?

A
  • Lectin domain

- EGF-like domain

45
Q

When and where is P-selectin induced?

A

During inflammation (tissue damage of infection)

In the endothelial cells

46
Q

What happens in the blood vessel upon infection?

A

Neutrophils have to leave the blood vessel - invade the tissue:

1) Neutrophils become adherent to the outside of the blood vessel wall - have a rolling behaviour
2) Once cells stop rolling - leave blood vessels and move between the endothelial cells

47
Q

What is the rolling behaviour of the neutrophills mediated by?

A

Selectins that are up-regulated during inflammation

Roll due to blood flow

48
Q

What is the movement of neutrophills into the endothelial cells mediated by?

A

Integrins

49
Q

What are the 2 different types of Ca2+ independant cams?

A

1) Secreted and part of the ECM

2) Have a transmembrane domain, intracellular domain and numerous repeats

50
Q

What are the kinds of repeats that Ca2+ independant cams can have?

A
  • Ig repeats

- Fibronectin type III domains

51
Q

How many different types of Ca2+ independant cams are there?

What are the main types?

A

Many different types

Main types: neural cell adhesion molecules (N-CAMs)

52
Q

How do Ca2+ independant cams arise?

A

From alternative splicing of a single gene to give rise to many different isoforms

53
Q

What binding do Ca2+ independant cams mediate?

A

Homophillic binding

54
Q

What confers the diversity of Ca2+ independant cams?

A

Highly glycosylated post-translationally

55
Q

What interactions do Ca2+ independant cams mediate?

A

Interactions between the ECM

Interactions between different cells

56
Q

Along with glycosylation, what is the other modification that occurs to Ca2+?

A

Have a SPECIFIC, VARIABLE polysialic acid modification

57
Q

What is the difference between immature cells and mature cells in the neural tube?

A

Immature:

  • Higher levels polysialic acid
  • Less adhesion
  • Can move around more

Mature:
- Less polysialic acid

BMS 242 - Advanced Cell and Molecular (24 decks)

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