Lecture 28 Flashcards
Give a classical example of where cell adhesion was studied
H.V. Wilson in 1907 identified that the cells of sponges can re-aggregate following dissociate from each other. Interestingly this was seen in a species dependent manner whereby cells of the same species would clump together sorting themselves into species
Transfection of L cells with cadherin family genes causes what
Homophilic binding between L cells expressing the same cadherins leading to adhesion
What are the two families of cell adhesion molecules
Ca2+-dependant and Ca2+ independent
Give an example of where cell adhesion molecules such as cadherins have roles other that in cell adhesion
VE-cadherin inactivation due to mutations causes abnormal vascular development and apoptosis of endothelial cells, indicating that it has roles in signalling
Explain the role of selectins in neutrophil trapping
The amount of selectins can be changed in endothelial cells and expression of them is found to be increased in an immune response. Selectins act to catch lymphocytes near to the site of inflammation which ultimately leads to an increase in diapedesis (crossing of the lymphocytes over the vessel wall).Catching by selectins allows other CAM molecules also present in the lymphocytes to adhere with the corresponding CAMs of the endothelial wall. This allows the lymphocytes to cross the vessel wall into the site of inflammation
Complex changes in selectin expression accompany the migration of neural crest cells, T or F
F – changes in cadherins do
What is seen if the cells of embryonic tissues that have been separated are reintroduced
They also re-aggregate into distinct clusters consisting of cells of the same type
What is significant about the number of genes involved in N-CAM expression
All of the N-CAM family of cell adhesion molecules are derived from a single gene. The original N-Cam transcript is subject to a vast array of alternative splicing and post translational glycosylation
What is meant by graded sorting
By varying the degree and levels of cadherin family gene expression, you can influence the degree of sorting of the cells expressing these genes
What can happen as a result of a failure of cell migration
Cell, tissue and organism dysfunction and death
Larger re-aggregates of cells tend not to reorganise due to the number of different interactions, T or F
F – in fact large re-aggregates do show organisation into distinct clusters based on cell type. In addition, these clusters begin to show regionalisation where particular cells have stuck together
What class of intracellular signalling proteins important in development have been found to bind to the intracellular domain of cadherins
Catenins (B-catenin)
What is the major family of Ca2+-independent CAMs
Neural cell adhesion molecules (N-CAMs)
Selectins are another type of cell surface membrane, Ca2+-dependant adhesion molecules. What attributes of cells do selectins recognise in order to elicit adhesion
Selectins recognise particular carbohydrate groups on proteins in neighbouring cells
Explain the role of polysialic acid in N-CAM adhesion
N-CAMs show variations in the amount of polysialic acid present as a post-translational modification. More post-translational modifications and polysialic acid is found in immature neurons which results in less adhesion
What happens following Ca2+ binding to cadherins
Causes a conformational change allowing interactions between cells
What is the significance of hypervariable protocadherins
These CAMs are thought to have roles in specifying synapses as wells as mediating neurite self-avoidance
Describe the basic structure of cadherins
Integral membrane glycoproteins that are 720-750 amino acids in length
Monoclonal antibodies have been instrumental in identifying the vast array of CAM variants due to their ability to their ability to distinguish between very similar proteins. Explain how monoclonal antibodies are made
Firstly, the specific antigen (protein or epitope) is injected into a different animal so that these animals mount an immune response. After a certain period the animals are euthanised and the lymphocytes are extracted from the spleen. These lymphocytes will be the cells synthesising antibodies for the target antigen and are fused with lymphoma cells to create hybridoma cells. Lymphoma cells are used as they are hyperproliferative and can survive indefinitely whereas the extracted lymphocytes dies quickly outside the body. They hybridoma cells are selected for due to their ability to survive in harsher mediums. Once isolated the hybridomas are separated into wells containing one cell each. These cells are then allowed to proliferate and give rise to a clonal population of cells all expressing exactly the same antibody targeted for a single epitope of the target protein.
Explain the significance of E and N-cadherin in the development of the early nervous system
Initially, only E-cadherin is expressed in the early embryo. However, newly formed mesodermal cells produced during gastrulation lose E-cadherin expression. Once the neural tube has formed this E-cadherin expression is replaced by N-cadherin
To which CAM family do cadherins belong and what are the other subfamilies are there
Cadherins belong to the Ca2+-dependent CAM family along with selectins and integrins
Cadherin family proteins only contain one Ca2+ binding site, T or F
F – they contain multiple
What are L cells
L cells are a cell line used for investigating cell adhesions. This is because they do not express any of the cadherin family of cell adhesion molecules
Give an example of where cell adhesion and migration play a vital developmental role
Formation of the early neural tube, the neural crest cells are required to detach from the dorsal neural tube, migrate, re-clump and then differentiate
How do selectins bind to target cells
The lectin domain of selectin binds to sugar groups present on the surface of these cells
