Cell adhesion 4

what process is essential for compaction

cell adhesion

specifically, which cadherin is essential for the formation of adherens junctions during compaction

E (epithelial) cadherin

where is E-cadherin localised

on the basolateral cell to cell contact, causing cells to lose their intercellular boundary

what happens when embryos are exposed to anti-cadherin antibodies

they fall apart

where is E-cadherin found

mainly in epithelial cells

where is N-cadherin found

expressed on nerve, muscle, and lens cells

where is P-cadherin found

in placenta and epidermis

what are the three key features of cadherin binding

cadherins like to bind to similar cadherins (homophilic), cadherin is calcium dependent so calcium is essential for two cadherins to bind, cadherin binding is relatively weak

which is the fact that cadherin binding is relatively weak important

it allows cells to break off and reform, this is important in both embryonic and adult tissues

what does the fact that cells from different parts of an embryo will sort out according to cell types mean

cells must be able to recognise other similar cells, suggesting that tissue architecture is actively maintained by differential affinities of cells for each other and the ECM

do L-cells normally express cadherins

no

what does the fact that levels of cadherin expression affects the affinity of cell to cell interaction mean

cells with higher cadherin levels form a strong interaction, more tightly compacted in the centre of the assembly

what type of cells express E-cadherin in development

ectoderm cells

what happens in terms of cadherin as the neural tube pinches off

cells turn off E-cadherin and turn on N-cadherin

what does over expression of N-cadherin in the migrating neural crest cause

leads to cells failing to leave the neural tube

once migrating neural crest cells turn off N-cadherin, which cadherin do they turn on

cadherin-7

what are the epithelial features

regular columnal morphology, high degree of cell adhesion, cell to cell junctions such as adherens, gap, and tight junctions, specialised apical membranes such as a brush border, underlying basement membrane, cells are relatively static

what are the mesenchymal features

irregular rounded or elongate morphology, loss of apico-basal polarity, front-back polarity, dynamic adhesion, lamelipodia and filopodia, cells are highly motile

what is epithelial to mesenchyme transition involved in

cancer cell invasion and is found in developing tissues

what are cancers arising from epithelial cells called

carcinomas

what does the basal lamina have the function of in breast cancers

restricting the migration of tumour cells away from the mammary duct

what do the tumour cells do to the basal lamina over time

they start to break it down

what can selectins bind to

carbohydrates

what are selectins expressed in

white blood cells and endothelial cells

what do infected cells do in terms of blood cells

they send cytokine signals to WBCs nearby

give an overview of WBC extravasion

WBCs receive a cytokine signal from infected cells, the white blood cells are able to bind to the selectins, this binding is weak and slows down WBCs, which start to roll, the white blood cells then start to express integrin, integrins mediate stronger adhesion and tissue invasion, leading to extravasion

what is extravasion

the process by which something moves out of a vessel into the surrounding tisse

what are leukocyte adhesion deficiency disorders caused by

molecular defects in selectin ligands, integrin expression, or activation on leukocytes

what are the characteristics of LAD-I

integrin proteins are absent or decreased, selectin ligands are normal, this leads to defective tight adhesion and invasion

what are the characteristics of LAD-II

integrin proteins are normal, there is a glycosylation defect in selectin ligands, this leads to defective initial binding and rolling

what are the characteristics of LAD-III

there is an activation defect in integrin proteins, selectin ligands are normal, this leads to defective tight junction adhesion and invasion

give an example of why the ECM must be degraded

to a allow WBCs to pass between endothelial cells

what are the two main groups of ECM degrading enzymes

matrix metalloproteinases (MMPs) which require calcium or zinc ions for activity, serine proteases which have a conserved serine residue in the active site

how is the activity of ECM degrading proteases kept tightly localised

some proteases are secreted in an inactive form, some proteases are confined by cell surface receptors, some proteases are inhibited by the actions of locally secreted inhibitors

what happens when tumour cells break away from the basal lamina

malignancy

what are CAFs (a type of fibroblasts) able to do

degrade the basal lamina by proteolytic ECM degradation

explain the process by which CAFs are able to degrade the basal lamina

they secrete MMPs, break the ECM and allow the tumour cells to escape from the basal lamina, non-proteolytic force mediated ECM breakage also occurs, the cells have integrin and are able to bind to the ECM and use force to break away the basal lamina, the tumour cells follow a collagen track after breaking free, CAF cells lead the way