Cell-cell adhesion Flashcards
Which transmembrane adhesion protein makes up adherens junctions?
cadherin
What is the intracellular cytoskeletal attachment of adherens junctions?
Actin filaments
Which transmembrane adhesion proteins make up desmosomes?
cadherin (desmoglein and desmocollin)
Which intracellular cytoskeletal attachment makes up desmosomes?
Intermediate filaments
Which cadherins are involved in homophilic binding?
classical and desmosomal cadherins (cadherin interacts with same cadherin on another cell)
Which cadherins are involved in heterophilic binding?
Fat cadherin (binds to dachsous)
Classical cadherins
What ions are cadherin-mediated adhesions dependent on?
calcium
What is the structure of cadherin?
Short intracellular domain
Long extracellular domain
5 cadherin repeats linked by short linker segments
What happens to cadherin structure in presence of low calcium?
Cadherin becomes flexible and hook-shaped
How does calcium stabilise cadherin?
calcium ions bind at interphase between cadherin repeat domains and linker segments
Do cadherins bind with low or high affinity? How can it become higher?
Low
Become high affinity through velcro principle.
Which protein groups connect cadherins to the actin filaments?
Catenins
Vinvulin
What are filopodia?
finger-like protrusions made of actin filaments
What do filopodia become after Rac?
Lamellipodia
What happens in adherens junctions assembly when Rac is deactivated and Rho is activated?
Formation of parallel bundles of actin filaments.
Formation of myosin bundles (contraction structures)
Which desmosome is a key adapter protein linking intermediate filaments to desmosomal cadherins?
desmoplakin
What is an important molecule in the transduction of mechanical tension by adherens junctions?
Alpha-catenin
During cadherin-cadherin binding, a pulling force occurs between cells.
What do the catenin proteins do at this time?
Extend to unfolded position.
Bind to vinculin.
Vinculin recruits more actin filaments.
What is the adhesion belt?
Adherens junctions lining the lumen of gut.
Linked to actin filaments, circling the inner edge of epithelial cells.
How does a sheet of epithelial cells become an epithelial tube?
Organised tightening of the adhesion belt.
Invagination of the epithelial sheet.
Pinching off of epithelial tube.
What is cadherin-dependent cell-sorting dependent on?
cadherin type
cadherin levels
Which cadherin is expressed by neuronal crest cells?
Cadherin 7
What are the four main functions of adherens junctions?
Tube structure formation.
Cell sorting.
Dynamic cell-cell adhesion
Signalling platforms
How does P120 catenin affect signalling of RhoA, NF-KappaB signalling and MAPK?
Blocks RhoA signaling
Blocks NF-kappaB signaling
Blocks the MAPK pathway
What pathway is beta catenin involved in?
Wnt signaling pathway
What does contact inhibition of cell proliferation ensure?
Tissue homeostasis
During cell density sensing, what protein does alpha catenin bind to?
Scaffold protein 14-3-3 in cell cytoplasm
Which protein does alpha-catenin/14-3-3 complex bind in the cytoplasm during cell density sensing?
Yap
What is Yap protein?
Transcriptional co-activator
Promotes cell growth
Can serve as oncogene when deregulated
Why does the alpha catenin-14-3-3 complex bind Yap when the cell is well connected via adherens junctions?
Bound Yap remains in the cytoplasm.
Prevents it from entering nucleus and promoting cell growth.
What does disruption of adherens junctions lead to (regarding Yap)?
The alpha catenin/14-3-3 complex releases Yap.
Yap is phosphorylated and enters nucleus.
When adherens junctions are disrupted and Yap is allowed to enter the nucleus, what does it bind to?
TEAD transcription factors
How is cell proliferation inhibited in hair follicles?
Dermal stem cells in Bulge remain quiescent in G0 until hair needs to be generated.
Cell density detected by alpha-catenin-dependent adherens junctions.
Which trans-membrane protein is involved in transient cell-cell interactions?
Selectins
What are the three types of selectins (and where are they found)?
L-selectins (Leukocytes)
P-selectins (platelet)
E-selectins (endothelial cells)
What are the three main domains of a selectin?
Lectin domain
EGF-like domain
Cytoplasmic domain
What do selectins bind to?
carbohydrates
Why are endothelial cells encouraged to express E-selectin during inflammation?
To attract WBCs expressing carbohydrates
Why is the adhesion between endothelial cells and leukocytes (via selectins bonding to carbohydrates) weak?
so leukocytes can roll along the endothelial cells surface to site of inflammation.
The weak adhesion and rolling of WBCs is selectin-dependent. The switch to strong adhesion is dependent on which protein?
Integrin
What are two examples of Immunoglobulin (Ig)-like superfamily CAMs?
NCAM (neural)
ICAM (intracellular) - important in WBC binding to endothelial cells
What is the main difference between cell-cell adhesion mediated by cadherins vs CAMs?
Calcium is required for cadherin-mediated cell-cell adhesions.
