Lecture 23- Cell polarity Flashcards
What is cell polarity?
The organisation of proteins inside and at the surface of cells, so that regions of the cell have distinct protein compositions allowing the cell to have different capabilities, morphologies and functions
Why is cell polarity important?
- Required for asymmetric cell division
2. As the cytoplasm is dense, polarity allows cells to bring components together and organise them
What did Whitman discover about polarity fields in 1878?
Studied leeches and showed that distinct cytoplasmic domains are differentially partitioned to descendants and that these differences were reflected in different cell lineages
What did Conklin discover about polarity field in 1905?
- Identified 5 different cytoplasm types that were differently inherited to determine tissue types
- Showed a region that looked different was ultimately confined to a subset of cells after a number of cell divisions
- Showed the formation of muscle cells and mesoderm were patterned at the early stages of ooplasmic segregation
What are the key functional requirements to be able to polarise a cell?
- Internal/external cues: signal sent to mark the need for an organisational change
- Marking the site: normally at the PM
- Decoding the site: sending a signal inside the cell to indicate something needs to happen
- Establishing the site: when more complexes are recruited to the site to allow the changes to occur
- Maintaining the site: duration will vary. Depending on what polarity has been established and why, the site may need to be maintained
What does cell polarity lead to changes in?
Changes in cytoskeleton organisation and membrane trafficking
Give 3 examples of where mechanisms can lead to cell polarity
- Asymmetric cell division
- Epithelial cell polarity
- Cell migration
Explain the establishment and maintenance of diverse cell shapes using common protein complexes
- Protein complexes build signalling centres that act as scaffold for small Rho-GTPases on specific membranes
- This control shape by regulating acto-myosin cytoskeleton and directing protein/vesicular trafficking
- These complexes are deployed in different combinations to yield distinct polarity outcomes
Explain how Rho-GTP is converted to Rho-GDP and vice versa
GAP proteins convert active Rho-GTP to inactive Rho-GDP
GEF proteins convert inactive Rho-GDP into active Rho-GTP
How were common protein complexes that are required to establish and maintain diverse cell shapes first identified?
In genetic screens in yeast, drosophila and C.elegans
Wha Rho-GTPase is essential for yeast to establish polarity?
Cdc42
Why must yeast generate cell polarity?
In order to grow and divide asymmetrically
Outline how budding yeast generate cell polarity
- Marking the sites: cortical membrane protein marks where a new daughter cell will be generated
- Decoding the site: signalling complex indicates a change needs to happen
- Establishing the site: Rho-GTPase Cdc42 gets activated and organises cytoskeleton and trafficking pathways
- Maintaining the site: feedback loops ensure complexes remain localised to ensure growth continues in the same part of the cell
What type of proteins form the core of cell polarity networks?
PAR proteins
How is the output of the cell polarity network established?
Established by opposing and complementary membrane domains that define a cells axis of polarity
How are PAR proteins maintained?
Set of proteins anteriorly and posteriorly which antagonise each other to maintain themselves
What was the cell polarity network first identified in?
C.elegans
Where is polarity first established in C.elegans?
The first asymmetric division on the zygote
How is asymmetric cell division and consequently cell polarity established in C.elegans?
- Polarisation starts with entry of sperm into the oocyte
- The position of sperm entry defines the posterior end of the zygote
- The zygote divides asymmetrically along the A/P axis
- This produces a larger anterior cell (AB) and a smaller posterior cell (P1)
- The daughters are different sizes and committed to different fates
What tissue types do AB and P1 cells give rise to and why are they different?
AB = ectoderm
P1 = mesoderm, endoderm and germ line tissues
Different tissues are generated as there is different distribution of PAR proteins at the end of cell division
How were PAR genes discovered?
- A genetic screen
2. In PAR mutants, the size and fate difference between daughter cells AB and P1 was less pronounced/identical
What do PAR genes encode and which protein is atypical and which is not conserved?
Par genes encode the par proteins PAR1-6
The 7th par protein is an atypical kinase called aPKC/PKC3
Par2 is not conserved
How is symmetry broken on fertilisation?
The sperm delivers a MTOC
How is the axis of polarity created post fertilisation?
Symmetry is broken on fertilisation when the sperm delivers the MTOC and defines the posterior pole
- The microtubules generated through the process of fertilisation recruit Par1/2 (posterior par proteins)
- This antagonises anterior Par proteins and they accumulate at the anterior cortical domain
- This results in the distinct localisation of par proteins
- Interactions between microtubules and the cortex results in pulling forces which act on the spindle causing the spindle to be de isolated towards the posterior end
- This causes the cleavage furrow to be generated asymmetrically giving rise to the size difference in AB and P1
- AB/P1 are different sizes and the cell fate determinants are unequally distributed at the point of cell division
