cell adhesion 4

what is the role of adherens junctions during compaction?

• compaction is a hallmark event of 9 cell stage mouse development

• previously observable intercellular boundaries become obscure as adherens junctions form

what are cadherins?

calcium dependent adherence proteins

what is the role of cadherins in compaction of the early embryo?

• E-cadherins are essential for formation of adherents junctions during compaction
• during compaction

what are the key experiments in adhering -mediated adhesion?

1) Adhesion blocking antibodies

• exposure to anti-cadherin antibodies causes the embryo to fall apart
  2) expression and deletion of cadherin
• mutant embryos lacking E-cadherins fall apart and die
• with non-adherent cells

what are the 3 types of cadherin?

• E- cadherin
• N - cadherin
• P- cadherin

where is E- cadherin expressed?

mainly on epithelial cells

where is N-cadherin expressed?

mainly on nerve

where is P- cadherin expressed?

mainly in placenta and epidermis

what is homophillic binding?

binding to similar cadherins

what is heterophillic binding?

binding to different cadherins

what is the role of cadherins and homophillic adhesion?

provides a mechanism by which cells can recognise and stick to similar cells

what occurs during cadherin-cadherin interaction?

• individual interactions are relatively weak
• collectively

what occurs during cell sorting according to origin?

• cells from different parts of an amphibian embryo sort out according to cell type
• cells must recognise each similar cells
• tissue architecture is actively maintained by different affinities off cells to each other (and the ECM)

what occurs during selective assembly of cells?

• L- cells don't usually express cadherins
• express specific cadherin genes in L-cells
• cells adhere to other cells expressing cadherins as distinct pools
• levels of cadherin expression affect affinity of cell-cell interactions
• cells with higher cadherin levels form stronger interactions so more compact assembly in center

how do cadherins and cell sorting work in development?

• Ectoderm cells express E-cadherin
• as neural tube pinches off

what are features of epithelial?

• regular columnar morphology
• high degree of cell adhesion
• cell-cell junctions
• apical membrane
• underlying basal membrane
• cells relatively static

what are features of mesenchymal?

• irregular rounded or elongated morphology
• loss of apico-basal polarity
• front-back polarity
• dynamic adhesions
• lamellipodia and filopodia
• cells highly motile

what occurs during epithelial to mesenchymal transition?

• assembly of cells into an epithelium is reversible - EMT
• EMT is found in developing tissues
• EMT is involved in cancer cell invasion

what are cancers arising from epithelial cells known as and how much do they account for of all cases?

carcinomas and 80%

what is the role of EMT in cancer invasion?

• cancers develop gradually from increasingly aberrant cells
• many cancers aren't diagnosed until late stage
• cancer metastasis accounts for around 90% of cancer cases
• cancers form when the basal lamina breaks down

what are selectins?

cell surface proteins that bind carbohydrates

what is the role of selectins?

• expressed in white blood cells and endothelial cells
• linked to actin cytoskeleton
• mediate transient cell-cell adhesions in the bloodstream

what is the role of selectins in inflammation?

• selectins mediate initial (weak) binding and rolling
• leukocytes activate integrals which recognise endothelial membrane proteins
• interns mediate stronger adhesion and tissue invasion

what is the role of leukocytes?

activate interns which recognise endothelial membrane proteins

what occurs when there defects in leukocyte adhesion?

• leukocyte adhesion deficiency (LAD) disorders are caused by molecular defects in selectin ligands

why must ECM be degraded?

to allow cells to pass between endothelial cells

what are the 2 groups of ECM degrading enzymes?

• matrix metalloproteinases (MMPs)
• serine proteases

what do matrix metalloproteinases require?

require bound Ca2+ and Zn2+ for activity

what are the role of serine proteases?

• have conserved serine residue in the active site
• some are highly substrate specific

what is the role of localised degradation of ECM?

• maintains overall ECM structure but creates space for migrating cells to pass through

how does tight localisation of ECM degrading proteases work?

• some proteases are secreted in inactive form
• localised activator converts them to active form
• some proteases are confined by cell-surface receptors
• some proteases are inhibited by actions of locally secreted inhibitors