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BISC 428 > Lecture 22 > Flashcards

Lecture 22 Flashcards

1
Q

What are the proteins that make up the junctions?

A

Transmembrane proteins
Cytoplasmic protens
Cytoskeletal elements (actin)

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2
Q

What are adherens junctions?

A

Fist junctions to form upon cell-cell contact

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3
Q

What is the function of adherens junctions?

A

Function: to adhere cells together

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4
Q

What are adherens junctions originally referred to as?

A

Originally referred to as Zonula Adherens/adhesion belt

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5
Q

What are adherens junctions characterized by?

A

Adherens junctions are characterized based on the transmembrane proteins that they use

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6
Q

What are the 2 different general types of transmembrane proteins?

A

1) Cadherins
2) Nectin (1-4)

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7
Q

What are the different types of cadherins?

A

E- Cadherin (Epithelia)
N- Cadherin (Neurons)
P- Catherine (Placenta)
T- Cadherin (Early embryos and neurons)
R- Cadherin (Retina)
M- Cadherin (Myotube)

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8
Q

What are the nectins (1-4)?

A

Nectin-like (Necl 1-5)

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9
Q

What was the first adherens junction transmembrane protein to be discovered?

A

E-Cadherin

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10
Q

How large was the first adherens junction transmembrane protein?

A

135kD

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11
Q

What are E-Cadherins?

A

A transmembrane protein
5 domains
Interact with identical proteins from the neughbouring cell
Calcium dependent interaction
E-cadherin binding is relatively weak
The strength to maintain the junctions lies in their association with actin

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12
Q

What are cytoplasmic binding proteins called?

A

Catenins

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13
Q

What are some cytoplasmic binding protein catenins?

A

Alpha, beta, gamma (AKA. Plakoglobin. It is also found at desmosomes), amd p120 catenin

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14
Q

What do catenins do?

A

Link the cytoskeleton to the transmembrane proteins

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15
Q

What else can catenin do?

A

Can act as asignaling molecules
B-catenin-wnt signaling pathway

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16
Q

What was thought of B-catenin?

A

For years the nuclear localization of B-catenin couldn’t be explained.
It was thought that it was a staining artifact

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17
Q

What does the crux of the Wnt signalling pathway involve?

A

The crux of the Wnt signalling pathway involves 3 things:
1) Accumulation of B-catenin in cytoplasm,
2) Translocation of B-catenin to the nucleus
3) Activation of transcription factors in the nucleus

18
Q

What are the 3 key proteins involved in signalling by junction proteins in Wnt?

A

1) Wnt
2) Frizzled
3) Dishevelled

19
Q

What is Wnt?

A

Extracellular ligand
Int: (1982) proto-oncogene. A “pre” cancer gene/gene product discovered by Harold Varmus’ Lab (Nobel Prize)
Wingless: already known protein in Drosophila known for cell polarity and embryonic development. Nobel prize given to Nusslein-Volhard and Weischaus
But Int and Wingless are the same proteins… so what do you do?
Combine them Wingless + Int= Wnt

20
Q

What is Frizzled?

A

Membrane receptor

21
Q

What is Dishevelled?

A

Cytoplasmic Protein

22
Q

What are some other crucial proteins?

A

The DESTRUCTION COMPLEX:
Axin
GSK3beta (Glycogen synthase kinase 3beta)
APC (Adenomatosis polyposus coli)
CK1alpha (Casein Kinase 1alpha)

23
Q

How was nectin discovered?

A

Was looking for novel actin associated proteins and found afadin

24
Q

What is afadin?

A

A 205 kD protein that binds to a variety of junction associated proteins; actin, ZO-1, vinculin, and others

25
Q

What are the two splice variants of afadin?

A

S- afadin
L- afadin

26
Q

What is S-afadin?

A

Expressed in neural tissue

27
Q

What is L-afadin?

A

Ebiquitously expressed
L-afadin contains one PDZ, three proline-rich regions, one F-actin-binding region (at the carboy-terminal)

28
Q

Where are nectins and cadherins found?

A

Nectins are found primarily at the adherens junctions, wheres cadherins are located along the lateral plasma memrbane in epithelial cells

29
Q

What do nectins bind to?

A

Nectins bind to afadin through the 4 most distal amino acids (E/AxYV) in the cytoplasm of nectins and the PDZ domains of afadin (Note: X is any amino acid)

30
Q

Why is the binding process required for nectin?

A

This is required for nectins to cluster at cell-cell junctions AND for a cadherin-catenin complex to be recruited to nectin based cell-cell adhesion sites

31
Q

What does this attach the nectins to?

A

This attaches the nectins to the actin cytoskeleton

32
Q

Do Necls bind to afadin?

A

Necls do not interact with afadin, but bind other proteins

33
Q

How do nectins interact?

A

Nectins homotypically interact in cis on the same cell and cis interactions are needed for the trans interactions for cell-cell binding.

34
Q

Are cis dimer interactions needed for Necls to trans interact?

A

It is unknown whether homotypic cis dimer interactions are needed for Necls to trans interact

35
Q

What is the strongest trans interaction for nectin binding?

A

Nectin-1 and Nectin 3

36
Q

What are the other Nectins that bind?

A

Nectin-3 and Nectin-5
Nectin-2 and Nectin-3

37
Q

Do nectins form primordial junctions?

A

Nectin forms primordial junctions in cells that don’t normally make junctions

38
Q

In what order does binding occur upon cell-cell contact?

A

Nectins bind first
Then E-Cadherin
Then JAM
(The Nectin/Cadherin/JAM adhesions intitially are interdispursed and mixed-up)
Then they start to segregate into tight junctions and adherens junctions once the claudins adhere

39
Q

What is the role of the nectins in contact inhibiton?

A

When 2 cells collide, Necl-5 on the surface of one cell will interact with Nectin-3 (obviously a trans interaction)
This will start the formation of a cell-cell junction
Then Necl-5 is down-regulated and endocytosed from the plasma membrane

40
Q

What does Nectin-3 do then?

A

Then Nectin-3 releases from Necl-5 and is kept on the plasma membrane where it will not interact with Nectin-1
Then cadherin is recruited

BISC 428 (23 decks)

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