Cell polarity Flashcards
Cell polarity
the organisation of proteins inside and at the surface if cells
regions of the cell have distinct protein compositions so it can have different capabilities, morphologies and functions
How is cell polarity generated?
cell surface landmarks adapting common pathways for cytoskeleton assembly
protein transport/membrane trafficking
What internal signals cause yeast to undergo significant morphological changes?
growth and division signals
What external signals cause yeast to undergo significant morphological changes?
pheromones for mating
nutritional signals like those for cell elongation
How can the budding events of yeast be followed?
staining cells with fluorescent dye called calcofluor which binds to component of yeast cell wall called chitin
allows sites of previous cell seperations to be seen as bright rings on cell walls
What controls where the position of new buds will be?
whether the cell is haploid or diploid
Haploid cell budding pattern
axial pattern
mother and daughter cells are constrained to form buds immediately adjacent to previous site of cell seperation
Diploid cell budding pattern
bipolar pattern
mother and daughter cells bud at the poles of the ellipsoidal cells
What genes have been identified in axial patterns?
BUD10
BUD3
BUD4
septins
What affect does mutations in axial genes have on the patten of budding?
mostly bud with bipolar pattern
What genes have been identified in bipolar patterns?
BUD8
BUD9
RAX2
components of actin cytoskeleton
What genes are required for both bipolar and axial patterns?
BUD1
BUD2
BUD5
What happens when BUD1,2 and 5 are mutated?
random budding pattern in haploid and diploid cells
all function together to signal to polarity establishment machinery the position of bud site landmarks
What proteins are important in polarity establishment?
Rho GTPase family
in yeast most important is Cdc42 which is highly conserved
Cdc42
small GTPase of the Rho family
regulated through cycles of activation and inactivation by binding partners Cdc24 and several GAPs
How does Cdc24 act on Cdc42?
it is its GEF- binds to active form of BUD1 at sites marked for budding
Cdc24 binds BUD1 and then activates Cdc42 to allow polarity site to be established so cell components can be trafficked to bud
How is cell polarity generated in order to mate?
haploid cells can polarise and redirect their growth axes in order to facilitate mating with partner
response is chemotropic due to pheromones being secreted by different cell types
MATalpha cells and MATa cells
MATalpha- secrete alpha-factor, which binds to MATa cells
MATa- secrete a-factor, which binds to MATalpha cells
How do daughter cells have different properties to mother cells?
myosins Myo2 and Myo4 are required for asymmetric inheritance of specific factors
How is backward movement of organelles in daughter cells prevented?
cargo adaptors are degraded
Why can’t yeast be used to understand intercellular interactions?
they are unicellular so can’t study growth of tissues and multicellular organisms
Candida albicans
benign member of mucosal flora but can cuase mucosal disease and become invasive
frequently seen in AIDS patients, premature babies and terminally ill patients
fungus can leave bloodstream and penetrate cells/tissues
How can candida albicans become pathogenic?
switch from yeast to hyphal form is stimulated at 37 degree by serum or neutral pH
hyphae are more adherent to mammalian cells and penetrate tissue
yeast cells taken up by macrophages can become filamentous and lyse it
yeast cells carried effectively in bloodstream promoting fungal dissemination in body
What are the two main routes to diversity?
polar mother cells divide to generate daughters that have inherited different components
daughters equal at birth become different by exposure to different signals/environments
Important steps in generating cell polarity and cell fate decisions
establishment of axis of polarity
mitotic spindle being positioned on axis
cell fate determinants being distributed differentially among daughter cells
Par proteins
form the core of a cell polarity network in many animal cells and in many developmental contexts
Asymmetric cell division in c.elegans
starts with entry of sperm into oocyte, position of this will define the posterior end of oocyte
divides asymmetrically along anterior posterior axis to produce larger anterior and smaller posterior cell
How does mutation in Par affect size and fate?
difference in cell size and fate between 2 daughter cells is less pronounces and can even be identical
How is symmetry broken during fertilisation?
when sperm delivers microtubule organising cell which becomes posterior pole and defines axis of polarity
How do the microtubules generated create the poles?
microtubules recruit Par 1/2 which antagonise anterior par proteins
they accumulate at anterior cortical domain
results in distinct localisations of par proteins
Where do the different par proteins go?
1/2- posterior
3/6- anterior
5- maintains boundary
How is the mitotic spindle organised?
interactions between microtubules and the cortex results in pulling forces which act on the mitotic spindle to be displaced toward the posterior end
Neuroblast division in drosophila
progenitor cells in a specific region of the epithelial monolayer called the ventral neuroectoderm
assymetric cell divisions give rise to small basal daughter cells called ganglion motor cells, and larger apical daughter cells
Hwo do ganglion motor cells and apical daughter cells divide differently?
GMC- only once more into a neuron and a glia cell
ADC- continue to divide asymmetrically
When is polarity established in drosophila?
when cell is delaminating and still in neuroectoderm
localise to apical region
in fully delaminated nueroblasts polarity is independent of surrounding cells
Drosophila cell fate determinants
transported in a basal direction to the ganglion mother cell
includes prospero and staufen
What are the three stages of cell migration?
protrusion
attachment
traction
Protrusion
pushing out of the plasma membrane in front of the cell
Attachment
the actin cytoskeleton inside the cell is attached via interacting proteins across the plasma membrane to the substratum
Traction
the bulk of the cell body is drawn forward through a process of contraction
What are the two different types of protrusion?
filopedia- dense core of bundled actin filaments uses Cdc42
lamallipodia- sheet like, broad structures uses Rac
Chemotaxis
the movement of cells toward or away from a signal such as a diffusible chemical
neutrophil moving to site of infection
How do neutrophils use chemotaxis?
receptors on surface of neutrophils detect low levels of bacterial peptides
peptides bind to GPCRs which triggers intracellular activation of G protein
leads to activation of Rac GTPase
leads to lamellipodial protrusion in direction of peptide gradient
When is de novo polarity set up in drosophila?
during embryo cellularisation
What are the effects of EMT?
loss of e cadherin
assymetric activation of small Rho GTPases
Cla4 + Ste20
PAK protein kinases
links polarity to cell cycle
Sec3
part of the exocyst complex
ensures polarised trafficking
Bni1
nucleate actin filaments
maintians polarity of cytoskeleton
