Lecture 18 Flashcards

1
Q

What do cells in multicellular organisms bind to?

A

Cells in multicellular organisms must be able to bind to other cells and to the extracellular matrix (ECM)

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2
Q

How do adhesion proteins do this?

A

Adhesion protein used to do this come from 5 categories:
1) Immunoglobulin cell adhesion molecules (IgCAMS)
2) Cadhesions
3) Integrins
4) Selectins
5) Mucins

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3
Q

How many IgCAMs are there?

A

There are hundreds of IgCAMs

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4
Q

What are IgCAMs?

A

They are receptors that bind to ligands on the surfaces of other cells

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5
Q

What can IgCAMs bind to?

A

Can bind:
Homotypically (to identical proteins on neighbouring cells) or heterotypically (to different proteins on neighbouring cells)
The differences in binding abilities specify interactions when developing mature animals

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6
Q

What is ‘CD’?

A

CD stands for “cluster of differentiation”
A commonly used nomenclature code
Use to classify cell surface genes recognized by monoclonal antibodies (without knowledge of the antigen)

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7
Q

How many extracellular immunoglobulin domains do they have?

A

Have 1-7 extracellular immunoglobulin domains (each domain has 90-115 residues)

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8
Q

What do IgCAMs dock into?

A

Docks into the plasma membrane using a single transmembrane helix

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9
Q

Are most IgCAMs a single polypeptide?

A

Yes, most are a single polypeptides

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10
Q

What does C-terminal have to do with IgCAMs?

A

C-terminal cytoplasmic tails are variable in sequence and in their ability to bind to different intracellular ligands

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11
Q

What does cellular expression of IgICAMs do?

A

It can change during development
This adds to the cellular adhesion specificity needed to generate organs

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12
Q

How many members of cadherins are there?

A

More than 80 members

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13
Q

What are cadherins dependent on?

A

Calcium-dependent for binding with “like” proteins on neighbouring cells

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14
Q

What type of interaction is this?

A

Thus, usually a homotypic interaction, but heterotypic interactions can also occur

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15
Q

What is the similar domain amongst cadherins?

A

CAD Domain

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16
Q

What does the CAD Domain consist of?

A

Consists of 110 residues arranged into a sandwich of 7 beta-strands

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17
Q

How do cadherins interact?

A

Cadherins usually interact head-to-tail through their N-terminal CAD Domains

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18
Q

What kind of interaction is formed?

A

Forms strong (trans) interaction with neighbouring cells “cis-interactions” happen with neighbouring cadherins binding (clustering) in the same cell

19
Q

What is the function of adaptor proteins?

A

Adaptor proteins (called catenins) are used to link the cadherions to the actin or intermediate filament cytoskeleton

20
Q

What is contact inhibition in cadherins?

A

When cells grow in culture they will continue to move and divide until stopped through signaling brought about primarily by cadherins
Cadherins attachment sends signals through the cell that ultimately causes the exclusion of transcription factors from the nucleus to block cellular proliferation
Cell movement is blocked by impeding the functions of the small GTPases

21
Q

What are the main receptors for extracellular matrix (ECM) adhesion?

A

Integrins
This bind to ECM proteins (fibronectin, collagen, laminin)

22
Q

What is the structure of integrins?

A

2 chains:
Alpha chain (18 in mammals) and
Beta chain (8 in mammals)
Form 24 different kinds of dimers
Contribute to ligand binding specificity

23
Q

What is ligant binding domain in integrins formed from?

A

2 globular heads

24
Q

What is integrin linked to?

A

Linked to 16nm legs and single transmembrane regions

25
Q

How do globular heads turn towards membrane?

A

The legs close in on themselves and globular heads turn towards the membrane when not bound to ligands

26
Q

How many binding partners does integrin have?

A

Integrin can have more than 1 extracellular binding partner

27
Q

How many integrins can ECM proteins bind to?

A

More than 1 integrin
Eg. Fibronectin binds at least 9 different integrins
Eg. Laminin binds at least 5 different integrins

28
Q

Is binding of integrins strong or weak?

A

The binding is weak, it allows cells to adjust their grip

29
Q

What does integrin do intracellularly?

A

Intracellularly, integrins associate with MANY signalling and structural proteins at structures

30
Q

What protein does snake venom contain?

A

Snake venoms contain small proteins called disintegrins

31
Q

What do they compete with?

A

Disintegrins compete with fibrinogen

32
Q

What is fibrinogen best known as?

A

Best known as a circulating protein in blood that is cleaved to make fimbrin (used for blood clots). Fimbrin is also an ECM protein

33
Q

What does snake venom compete with?

A

Snake venom competes with Fimbrin, Fibronectin and other ECM proteins for integrin binding sites on many cell types including platelets; blocking integrin cell adhesion

34
Q

What are selectins?

A

Commonly used primarily by white blood cells and platelets (other cells use them too)

35
Q

What are the 3 selectins?

A

E (endothelial)
L (lymphocyte)
P (platelets)

36
Q

What is selectin used to do?

A

Used to grab circulating white blood cells allowing them to roll, slow down and exit the blood to enter tissues

37
Q

What is selectin dependent on?

A

All selectins have a calcium dependent actin domain at the very end of the protein (these can be thought of as receptors)

38
Q

What does the calcium dependent actin domain bind to?

A

Binds to sugars (oligosaccharides and fucose)

39
Q

What are ligands?

A

Mucin-like glycoproteins on endolethial cells (cells lining blood vessels) and on white blood cells

40
Q

What kind of binding affinity does selectin have?

A

Low affinity (weak) binding… they bind and release quickly (allowing slowing and rolling)

41
Q

What happens when selectin is bound?

A

When bound, they have a high tensile strength
Not very selective as to which oligosaccharides they bind to

42
Q

What are mucins?

A

Highly negatively charged proteins
Extend up to 50 from the cell surface

43
Q

Where are mucins found?

A

Found on endothelial cells, white blood cells, the surface of the respiratory tract and gastrointestinal tract

44
Q

What do mucins interact with?

A

Interact with selectins