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Advanced molecular & cell L2 > Lecture 15 - establishment of apical basolateral polarity in health & disease > Flashcards

Lecture 15 - establishment of apical basolateral polarity in health & disease Flashcards

1
Q

What does cell polarity generate?

A

a wide variety of forms, allowing a diverse array of function

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2
Q

What is cell polarity?

A
  • organisation of proteins at the plasma membrane and inside cells
  • regions of the cell have distinct protein compositions
  • allows different capabilities, morphologies & functions
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3
Q

What are the 2 main routes to generate diversity through polarity & cell fate decisions?

A
  • Polar mother cells divide to generate daughters that have inherited different components
  • Daughters could be equal at ‘birth’ but then become different by exposure to different environmental signals
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4
Q

What is a historical perspective into polarity in development and early cell fate determination?

A

Whitman (1878) - distinct cytoplasmic domains are are differently partitioned to leech descendants and that these differences were reflected in different cell lineages

Conklin (1905) - identified 5 different cytoplasm types in the ascidina (sea squid) oocyte that were differentially inherited to determine tissue types

These studies laid the foundations of modern developmental genetics & biology

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5
Q

What model organisms are widely used to understand cell fate decision?

A

C.elegans & Drosophila

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6
Q

What model organism is used to understand polarisation?

A

C.elegans (type of roundworm)

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7
Q

What arises after particular asymmetric divisions?

A

There are particular lineages that arise after particular asymmetric divisions, which leads to different tissues.

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8
Q

How is polarity established in the C.elegans embryo?

A
  • P0
  • AB & P1
    P1: EMS & P2
    EMS: MS & E
    P2: C & P3
    P3: P4 & D
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9
Q

What is the molecular machinery which establishes apical basolateral polarity?

A
  • a genetic screen to identify key players in this asymmetric division led to the discovery of the PAR genes (for partitioning defective)
  • in PAR mutants, the size & fate differences between cells AB & P1 are less pronounced and in extreme cases the 2 are identical
  • The par genes encode the par proteins Par1-6 and the 7th member of the group is atypical protein kinase C (aPKC). Only Par2 is not conserved in other metazoans
  • 7 members in PAR family and highly conserved
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10
Q

When is symmetry broken?

A

Following fertilisation

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11
Q

How is symmetry broken following fertilisation?

A
  • Sperm entry point defines the posterior pole and the axis of polarity
  • Sperm delivered a microtubule organizing centre (MTOC)
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12
Q

What does the sperm entry point define?

A

Defines the posterior pole and the axis of polarity

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13
Q

What does sperm deliver?

A

microtubule organizing centre (MTOC)

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14
Q

How is polarity established in the embryo?

A

PAR protein complexes mediate polarity through a negative feedback loop

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15
Q

What are features of PAR proteins and cell polarity networks?

A
  • PAR proteins form the core of a cell polarity in many animal cells and in many developmental contexts
  • the output of the network is one of mutual antagonism with the establishment of opposing and complementary membrane domains that define a cell’s axis of polarity
  • The network was first identified in C.elegans, however useful, as well conserved throughout evolution
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16
Q

What maintains polarity?

A

Mutual antagonism

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17
Q

Summarise PAR proteins and embryo

A
  • PAR proteins reliant on cytoskeleton to maintain polarity
  • Microtubules recruit Par1 & Par2 to the posterior cortex
  • Antagonises anterior Par proteins which accumulate at anterior cortical domain
  • Distinct localization of the Par proteins, Par3/Par6/aPKC localize to the anterior cortex, Par1 & Par2 are at the posterior cortex and Par5 maintains the boundary
  • phosphorylation is key in the feedback loops that allows poles to be defined
  • Interactions between microtubules and the cortex results in pulling forces, which act on the mitotic spindle which causes the spindle to be displaced TOWARDS the posterior end.
  • redistribution of the Par proteins and cell fate determinants requires a directional and actin-myosin based process
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18
Q

What are PAR proteins reliant on?

A

PAR proteins are reliant on cytoskeleton to maintain polarity

19
Q

What is the key to cell polarity?

A

The cytoskeleton

20
Q

What does actin do in microvilli?

A

Enhance the ability of gut to absorb components.

21
Q

What do microtubules allow in microvilli?

A

Microtubules allow transportation

22
Q

What do intermediate filaments contribute to microvilli?

A

Intermediate filaments contribute to the structural support of the cell.

23
Q

How does polarity in bacteria occur?

A
  • plasmid segregation
  • ParM ensures that plasmid segregation occurs in the correct formation
24
Q

What do junctions in epithelial cells allow?

A

Junctions in epithelial cells establish polarity through interaction with the cytoskeleton

Junctions are key in establishment of epithelial cells. Apical domain faces the environment - e.g. skin, nasal passages, gut - tight epithelium. Basolateral domain - faces inwards & connected to basal laminae, which is a thin layer of extracellular matrix. Architecture of cell based on junctions.

25
Q

What are the 4 different types of junctions?

A
  • Tight junctions
  • Adherens junctions
  • Desmosomes
  • Gap junctions
26
Q

What are tight junctions?

A

Tight barrier between epithelial cells, preventing movement of many molecules across the barrier. Some can move through paracellular transport e.g. ions

27
Q

What are adherens junctions?

A

Connects actin filament bundle in one cell with that in the next cell

28
Q

What is a desmosome?

A

connects intermediate filaments in one cell to those in the next cell

29
Q

What are gap junctions?

A

allows the passage of small water-soluble molecules from cell to cell

30
Q

What are the links from the cytoskeleton to the extracellular matrix?

A

These junctions bring the membrane together and decide how permeable the junction is

31
Q

What are junctions important for?

A

Junctions are important for the barrier function of epithelia

32
Q

What is a good experiment to show how good epithelia is at acting as a permeability barrier?

A

Placing a tracer molecule on one side of the membrane and seeing if it flows past the junction (or not).

33
Q

What are cadherins important for?

A

Tissue organisation & the formation of junctional complexes

34
Q

What does a xenopus embryo develop into?

A

Develop into neural plate, mesoderm and epithelial cells

35
Q

What do cadherins have a role in?

A

key role in tissue organization

36
Q

What is the affinity between cadherins?

A

Interactions between cadherins have a low affinity - so junctional complexes have low affinity, however there are a lot of interactions leading to overall high affinity

37
Q

What does immunofluorescence allow?

A

It allows us to visualise apical & basolateral domains and junctional complexes

38
Q

What does transcellular transport of glucose rely on?

A

Cell proliferation

  • Composition of membranes have to be different to perform tasks like uptake of glucose in gut. Symporter needs to be in apical membrane
39
Q

What membrane is the symporter found in, for uptake of glucose to occur?

A

Apical membrane

40
Q

What is a symporter?

A

A symporter is a type of membrane transport protein that moves two or more molecules across a cell membrane in the same direction

41
Q

What does the maintenance of polarity rely on?

A

Endocytosis, secretion & recycling

  • Vesicle trafficking contributes to the establishment of polarity
  • Delivery of material to the correct domain by secretion, endocytosis & recycling
42
Q

Describe key features to development and tissue remodeling

A
  • apical basal cell polarity is essential for functional epithelial
  • cell polarity is lost in advanced tumours - invasive & malignant properties
  • Metastasis is the largest killer in cancer
  • Maintenance of cell polarity is highly dynamic - interference of human cancers is epithelial in origin
43
Q

What does a loss of polarity lead to?

A

Malignancy

Advanced molecular & cell L2 (28 decks)

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