General cellular communication

Question 1

Gap junction - definition and function

Answer 1

• Gap junctions are narrow water-filled channels that directly connect the cytoplasms of adjacent cells (all cells except mobile and skeletal muscle cells)
• The channels allow the exchange of inorganic ions and other small water-soluble molecules such as cAMP and calcium
• Bidirectional with the aim to homogenize conditions

Question 2

Gap junction - structure

Answer 2

• Gab junctions are made from plasma membrane proteins called connexins of which we have many isoforms
• The connexins have 4 transmembrane domains
• 6 connexin proteins assemble in the plasma membrane of a cell to form a connexon/hemichannel
• When 2 identical connexons of adjacent cells come in contact they link up and form a gab junction

Question 3

Anchoring junctions - definition and types

Answer 3

• Anchoring junctions connect cells to each other and to the basal lamina (in case of epithelial cells) and are essential for barrier formation, flexibility, movement, strength, heart function, etc.
  1. Occluding junctions = tight junctions seal the membranes of 2 cells
  2. Cell-cell anchoring junctions = adherens junctions connect actin filament bundle from 1 cell with the next and desmosomes connect intermediate filaments form neighbouring cells
  3. Channel-forming junctions = gab-junctions
  4. Cell-matrix anchoring junctions = hemidesmosomes connect intermediate filaments of the cell to the basal lamina and actin-linked cell-matrix adhesion (focal adhesion) anchors actin filaments to the ECM

Question 4

cell-cell anchoring junction structure

Answer 4

• Adhering junctions consist of:
  • Extracellular domain (adhering protein): E-cadherin
   There is also N and P cadherin but these are not in epithelium but in neuro and placenta
  • Adaptor proteins: alfa-catenin and beta/gamma-catenin
  • Actin
• Desmosomes consist of:
  • Non-classical cadherins: desmoglein and desmocolin
  • Adaptor proteins: plakoglobin, plakophilin and desmoplakin
  • Desmin/intermediate filamants

Question 5

Cell-ECM junctions - structure

Answer 5

• Hemidesmosomes consist of:
  • Extracellular domain: integrin afa6beta4, collagen XVII
  • Adaptor proteins: plectin and dystonin
  • Keratin
• Focal adhesion consist of:
  • Integrins
  • Many adaptor proteins (14) including talin, FAK, tensin and vinculin
  • Actin

Question 6

occluding/tight junction - structure

Answer 6

• Consist of:
  • Claudins (mainly) and occludins (as support together with junction adhesion molecules/JAMs)
  • Adaptor: ZO proteins
  • Actin

Question 7

4 types of signalling

Answer 7

1. autocrine (intracrine)
2. paracrine
3. juxtracrine
4. endocrin

Question 8

Notch signalling

Answer 8

• Signalling between adjacent cells via Notch and Delta (or Delta-like ligands) regulates cell fate choices in many tissues and animals and during development
• Juxtracrine signalling
• Often, it mediates lateral inhibition to control the formation of mixtures of differentiated cell types within a tissue
  1. When activated by the binding of Delta on another cell, a plasma membrane-bound protease (Adam10) cleaves off the extracellular domain
  2. Gamma-secretase cleaves of the cytoplasmic tail of Notch
  3. The released tail translocates into the nucleus to activate the transcription of a set of Notch-response genes.

Question 9

wnt signalling

Answer 9

• Paracrine and autocrine
• No wnt –> LRP and frizzled and dishevelled are not active leaving the destruction complex (axin, APC, GSK3 and CK1) active preventing beta-catenin accumulation by phosphorylating it and tagging it for ubiquitination
• When there is wnt, there is active frizzled and LRP breaking down the destruction complex. This causes stable beta catenin to accumulate and go to the nucleus to release inhibition proteins (groucho) from wnt genes

Question 10

Shh signalling

Answer 10

• paracrine and autocrine
• abscence of shh: patched keeps smoothened inactive which prevents the recruitement of costal2/fused/Ci and thereby stimulates the phosphorylation (by PKA, GSK3 and CK1) and breakdown of the Ci protein via the UPS which produces Ci fragments that act as transcriptional repressors
• presensce of shh: wnt binds to iHOG and patched which causes smoothened to be phophorylated by PKA and CK1 which causes the costal2/fused/Ci complex to be recruited preventing Ci processing. The intact Ci protein then acts as transcriptional activator