Cell polarity Flashcards
Why is cell polarity necessary?
For cells to generate forms with a diverse array of functions
Create distinct protein compositions. giving different cell capabilities and functions
What are cell surface landmarks important for?
Adapting common pathways for cytoskeleton assembly, protein transport and membrane trafficking.
This creates cell polarity
Outline a general pathway to form a polarity axis
- Marking the site (usually binding to something)
- Decoding the site (signalling)
- Establishing the site (recruiting machinery)
- Maintaining the site (Keeping machinery in place)
What creates a polarity axis?
Changes in cytoskeleton and vesicle formation
What yeast is used to study polarity and why?
Saccharomyces cerevisiae
Entire genome sequence is annotated so can be used to track genes
Has been used to understand cell cycle, secretion and polarity
Give an internal signal for polarity
Growth and division signals
Give an external signal for polarity
Pheromones for mating and nutritional signals
What structures form when yeast cells bud and divide?
Spatial patterns- axial, bipolar
How are yeast budding events tracked?
Calcofluor which binds to chitin
These show birth scars where sites of previous cell divisions are marked as bright rings on the cell wall
How are yeast budding events tracked?
Calcofluor which binds to chitin
These show birth scars where sites of previous cell divisions are marked as bright rings on the cell wall
What does the position of a new bud on yeast depend on?
Cell type (haploid/diploid)
What sort of yeast cells bud in an axial pattern? (mother and daughter cells form buds adjacent to the previous site of cell separation)
Haploid a and α cells
What sort of yeast cells bud in a bipolar manner? (mother and daughter cells bud at the poles of their ellipsoidal cells
Diploid cells. This contains the pattern to adapt more advantageously
What genes are involved in marking a mother yeast bud neck during a cycle for budding in the next cycle?
BUD3
BUD4
BUD10
septins
What do mutations in BUD3, BUD4 and BUD10 in haploid yeast cells cause?
Change budding to a bipolar pattern
What do mutations in BUD8, BUD9 and RAX2 in yeast cause?
Disrupt the bipolar budding pattern
What genes encode the ends of diploid yeast cells?
BUD8
BUD9
RAX2
What genes encode proteins that decode axial and bipolar marks in yeast?
BUD1
BUD2
BUD5
What do mutations in BUD1, 2 and 5 cause in yeast?
Random budding pattern of haploid and diploid cells
What Rho-GTPase families are important in establishing a yeast polarity site?
Cdc42
Cdc43
Cdc24
Explain what Cdc42 is
small rho GTPase
Activated by Cdc24 binding to the marked budding site and activating Bud1.
Cdc42 then establishes the polarity site
How do haploid yeast allow mating?
They polarise and redirect growth to allow them to mate with a partner.
Give a mechanism of how Cdc42 is activated
- Bud1 has GTP added by Bud5 (its GEF)
- Bem1 generates new actin filaments to drug Cdc24 to inactive Cdc42
- Cdc24 acts as a GEF and acitvates Cdc42
What proteins are required for asymmetric inheritance of certain factors in yeast?
Myo2
Myo4
What is cell polarity critical for?
Asymmetric cell division
Epithelial cells (barrier)
Cell migration
What was Whitman’s 1878 hypothesis of yeast cells generating daughter cells?
Distinct cytoplasmic domains are differentially partitioned, differences reflected in different cell lineages
What was Conklin’s 1905 hypothesis of yeast cells generating daughter cells?
5 cytoplasmic types of ascidna oocyte that are differentially inherited to determine tissue types
What are Candidasis and Candidaemia?
Benign members of mucosal flora
Yeast overgroeth can cause oral/vaginal thrush
Can have 30-50% fatality if it becomes infectious in the bloodstream
Candida switch between yeast and hyphal form (adhere to mammalian cells and penetrate)
What are the two ways diversity is established in yeast
Intrinsic: polar cells divide to generate daughter cells that have inherited different components
Extrinsic: Daughter cells can be equal at birth but differentiate due to environmental signals
What do PAR proteins do?
Recognise and localise cell material
Define a cell’s polarity axis via mutual antagonism by opposing and complementary membrane domains
How is the anterior-posterior axis established in oocytes?
The position of entry of sperm into the oocyte determines the posterior end.
The oocyte splits into a smaller posterior cell P1 and a larger anterior cell AB.
What do par genes encode?
par1-6 and atypical PKC (aPKC (PKC in C. elegans)).
What par protein is conserved in yeast but not other metazoans
Par2
Outline how par proteins are involved in creating the anterior-posterior axis
- Symmetry is broken in fertilisation when sperm delivers a mitotubule organising centre (MTOC)
- Microtubules recruit Par1 and Par2 to anterior par proteins to the anterior cortical domain
- Par3/Par6/aPKC localise to the anterior cortex, Par1 and 2 localise to the posterior cortex
Par5 maintains the boundary - Microtubules pull on the cortexes, displacing mitotic spindles to the posterior end
- Par proteins redistribute, determining cell fate
How do CNS progenitor cells (neuroblasts) undergo cell division?
Rounds of asymmetric cell division give rise to a small basal daughter cell (ganglionic mother cell) and apical daughter cell
GMCs divide to give a neuron and glia cell.
Apical daughter cells divide asymmetrically to produce another GMC
What happens when neuroblast delaminate (split into layers)?
Par3, Bazook/Par6 are found in a stalk that extends into the epithelium
Baz/Par6 localises into the apical region
Baz anchors Insc/Pins at the membrane to orient the mitotic spindle
The scribble complex helps spindle alignment
Outline the epithelial polarity programme (EPP)
Epithelium is the first tissue formed after an egg is fertilised
Epithelial cells have a polarised actin cytoskeleton, allowing the apical surface to constrict, important in gastrulation and tubulation
How do epithelial cells generate diversity?
They can orient their mitotic spindle to allow division parallel to the epithelial sheet
They can have an epithelial-mesenchymal transition (EMT) to non-epithelial cells
or mesenchymal-epithelial transition (MET) back to epithelial
What are two of the main complexes that interact with the Par complex to form polarity in Drosphila?
Crumbs/CRB complex
Scribbled/SCRIB complex
How can invertebrates maintain apical-basolateral polarity?
Tight junctions are formed, maintaining this polarity through homophilic interactions
How can invertebrates maintain apical-basolateral polarity?
Tight junctions are formed, maintaining this polarity through homophilic interactions
What happens in an epithelial-mesenchymal transition?
Signals lead to a loss of E-cadherin, leading to EMT
Apical-basal polarity axis is converted to a migration axis which has front-rear polarity
Asymmetric activation of small Rho GTPases (Cdc42 and Rac1 at the front, RhoA at the rear)
Outline the steps in cell locomotion
- Protrusion: the plasma membrane is pushed out in front of the cell
- Attachment: actin cytoskeleton is attacked via proteins across the plasma membrane to the substratum
- Traction: cell body is drawn forward through contraction
What are the main structures in actin
RAK activates filopedia (microspikes with a actin bundles) and lamellipodia (short, cross-linked actin)
Stress fibres are activated by small GTPases and involved in contractility
What is chemotaxis
Movement towards a diffusible chemicale,g movement of neutrophils towards a bacterial infection
