Lecture 22 – Cell-cell Interactions

Q: What role do materials outside the plasma membrane play?

Regulating tissue development, wound healing, and fighting infection.

Q: What are the two common methods of cell-cell interaction?

Receptor-ligand interactions and direct cell-cell contact.

Q: What six processes require cellular interactions?

Intercellular communication, survival, tissue strength, organ function, immune system function, embryonic development.

Q: What are the four families of integral membrane proteins that mediate cell-cell adhesion?

Selectins, immunoglobulin superfamily (IgSF), integrins, and cadherins.

Q: What are cadherins and what do they depend on?

Calcium-dependent adhesion proteins that bind a cadherin on a neighbouring cell. An important factor in molding cells into cohesive tissues during embryonic development and holding them together in the adult.

Q: What types of junctions are cadherins distributed along?

Synapses, adherens junctions, and desmosomes.

Q: How do cadherins contribute to embryogenesis?

Cells from different germ layers (e.g., ectoderm and mesoderm) display distinct adhesive properties via cadherins, and selective cadherin-cadherin interactions help establish the spatial order of different tissues in the embryo.

Q: What did experiments with separated embryonic cells show about cadherins?

Separated cells would redistribute themselves so that each cell adhered only to cells of the same type, demonstrating selective cadherin-mediated adhesion.

Q: What is the relationship between cadherins and cancer?

Loss of E-cadherin is associated with malignancy and the metastatic spread of cancer. E-cadherin is one of the most important proteins that reduces metastasis.

Q: What was shown by injecting human iPSCs into a developing pig embryo?

The human cells successfully integrated into the pig's developing tissues, demonstrating that human and pig cells could interact appropriately through their cadherins.

Q: What are the key features of the immunoglobulin superfamily (IgSF)?

Immunoglobulin domains, mediate calcium-independent cell-cell adhesion, interact homotypically (IgSF–IgSF, e.g., two L1 molecules) or heterotypically (IgSF–integrin).

Q: What are ICAMs, and what other types of IgSF proteins exist?

Intracellular adhesion molecules (a type of IgSF). Other types: NCAMs (neural) and VCAMs (vascular). Integrins act as receptors for ICAMs in heterotypic interactions.

Q: What are selectins and what do they depend on?

A family of calcium-dependent membrane glycoproteins that bind to specific oligosaccharides; contain a lectin-like domain (binds specific carbohydrate groups).

Q: What are the three types of selectins and where are they found?

E-selectin on endothelial cells, P-selectin on platelets and endothelial cells, and L-selectin on all types of leukocytes (WBCs).

Q: What is a neutrophil and what can it do?

A type of white blood cell in the bloodstream, can phagocytose bacteria, migrate from blood vessels into tissue during infection.

Q: Where do leukocytes adhere and extravasate — veins or arteries?

Surface of veins; they do not crawl out of arteries.

Q: What are the five steps of transendothelial migration during inflammation?

1) Inflammation activates endothelial cells, which upregulate selectins.

2) Selectins bind carbohydrate residues (Psgl-1) on the neutrophil, causing rolling.

3) Platelet activating factor or IL-8 on the endothelial surface activates GPCRs on the neutrophil, which activates integrins.

4) Activated integrins bind ICAMs on the endothelial surface, triggering cytoskeletal rearrangement.

5) The neutrophil undergoes transendothelial migration (extravasation) out of the vessel.

Q: Which adhesion protein families are calcium-dependent and which are calcium-independent?

Cadherins and selectins are calcium-dependent. IgSF proteins are calcium-independent. Integrins interact with IgSF proteins (ICAMs).

Q: What is the difference between homotypic and heterotypic adhesion interactions?

Homotypic interactions: between two identical proteins (e.g., two L1 IgSF molecules). Heterotypic interactions: between different proteins (e.g., an IgSF protein binding an integrin).

Q: What is metastasis?

The spread of cancer cells from the original tumour to other parts of the body. Cancer cells escape normal growth controls, and loss of adhesion proteins like E-cadherin allows them to break free and spread.