Cell adhesion, migration and motility (L7) Flashcards
Why are cell adhesion molecules important?
CAMs are important because they allow cells to migrate and aggregate. Failure to do this leads to cell, tissue and organism dysfunction and death. E.g. failure of neural crest cells to delaminate and migrate - means no formation of neurones. or when inner cell mass cells and trophoblast adheres to the endometrium in mammals.
What are the classical studies of cell aggregation?
Classical cell aggregation (H.V. Wilson) shows sponges can reaggregate, and also if you mix tissues from multiple species they reorganise themselves. Embryonic tissue also resorts by tissue and in large reaggregates, you can see regionalisation
What are L cells and what were they used for?
A cell line that doesn’t express cadherins so helped lead to their discovery. It was found that the cells didn’t aggregate at all, so were useful for transfecting certain cadherins to find their specific role. Transfection of cadherins includes homophilic sorting - where cells expressing different types of cadherins aggregate with the same ones. If you express different levels of the same cadherin you also get graded sorting, where those expressing similar levels aggregate together. This is important in general cells principle
What are cadherins?
Integral membrane glycoproteins. 720-750 amino acids
They’re anchored in the plasma membrane. Calcium causes conformational change which allows for binding between cells. The cadherins are arranged in certain orientations and perpendicular arrays act like velcro. Different arrangments are localised to different regions of the cells. The arrangement of cadherins, therefore, dictates the orientation of the cell.
What are the different types of cadherins?
There are over 100 types of cadherins. Epithelium cadherin (E-cadherin) is the most studied. Its the first ones to be expressed in embryos. Different cadherins are very variable in structure, however classical cadherins all have one transmembrane domain and repeated extracellular domains. Protocadherins are found in the NS and are highly variable. Adherens in junctions hold cells together.
Explain the different expression patterns of cadherins
The expression of cadherins is very complex, it can be in strict boundaries or graded. Some boundaries also overlap. E.g. in the brain there are some areas that express multiple isoforms of protocadherins (made by alternative splicing). They may have a role in specifying synapses and neurite self-avoidance.
What are catenins?
Catenins are intracellular proteins that link to actin. Beta catenins can regulate proliferation via c-myc
Catenins have signalling roles when interacting with cadherins. They bind intracellular cadherins to the cytoskeleton
What is the structure of cell junctions?
Junctions between cells are built through an interaction between myosin and actin. When myosin binds to actin, it pulls it down, extending alpha-catenin and exposing the vinculin binding site, which then also allows for cross-linking between more actin sites. These interactions, when stable, give rise to the whole cytoskeleton. The tension between cadherins is what etends the alpha catenin
Explain how catenin helps regulate the cytoskeleton
Catenins can sense when cells are interacting with neighbouring cells due to the tension created. Changes occur through activation of Rho via beta-catenin. Mutations in Rho affect the actin cytoskeleton. Constitutively active Rho leads to stress fibre formation (very stringy and organised filaments) which make the cell very rigid.
How do cadherins contribute to the early nervous system?
Only E-cadherin is expressed in the early embryo. It is used to hold cells together in the compact stage. Newly formed mesoderm cells lose E-cadherin and also for complex changes in neural crest cell formation (N-cadherin replaces E-cadherin)
What are selectins?
They are on the surface of the cell with a single transmembrane domain. They bind to carbohydrates on neighbouring cells. They are calcium-dependent and have repeating sequences in the extracellular domain like cadherins. They don’t interact with other selectins. Selectins are also anchored to actin - so its strong enough not to break during cell shape change. Selectins are used in neutrophil trapping - so white blood cells can escape the blood vessel and get into the tissue. Weak adhesion is selectin dependant and string adhesion is integrin dependent. The white blood cells roll along the vessel using selectin
Explain calcium-dependent CAMs do
There are numerous calcium-dependent CAMs. The major forms are the cell adhesion molecules N-CAMs. They mediate interactions with the ECM as well as other cells. homophilic binding. They arise via alternative splicing and post-translational glycosylation. They’re highly glycosylated. They the neural tube, there is more polyasylic acid which therefore creates less adhesion meaning cells can move around more. Therefore, they are more in immature cells
